1
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Gonzalez-Riano C, León-Espinosa G, Regalado-Reyes M, García A, DeFelipe J, Barbas C. Advanced lipidomics using UHPLC-ESI-QTOF-MS/MS reveals novel lipids in hibernating syrian hamsters. J Chromatogr A 2025; 1743:465692. [PMID: 39864223 DOI: 10.1016/j.chroma.2025.465692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/16/2025] [Accepted: 01/16/2025] [Indexed: 01/28/2025]
Abstract
Mammalian hibernation offers a unique model for exploring neuroprotective mechanisms relevant to neurodegenerative diseases. In this study, we employed untargeted lipidomics with iterative tandem mass spectrometry (MS/MS) to profile the brain lipidome of Syrian hamsters across different hibernation stages: late torpor, arousal, and euthermia (control). Previously, a lipid species identified as methyl-PA(16:0/0:0) showed a significant increase during torpor, but its precise structure was unresolved due to technological constraints. Leveraging iterative MS/MS and advanced lipid annotation tools (LipidAnnotator and MS-DIAL), we accurately annotated 377 lipid species, including the re-identification of methyl-PA(16:0/0:0) as methylated lysophosphatidic acid (PMeOH 16:0/0:0). This reannotation led to the discovery of two additional lipids during torpor: PMeOH 18:0/0:0 and PMeOH 18:1/0:0. Verification involved manual inspection of MS/MS spectra and Kendrick Mass Defect plots. The lipid alterations observed during torpor suggest biochemical adaptations to maintain membrane fluidity and protect against oxidative stress under hypothermic conditions. Elevated levels of PMeOH lipids and their lyso-forms may play roles in cell survival signalling. Additionally, a decrease in phosphatidic acid species and an increase in diacylglycerol species imply a metabolic shift favouring diacylglycerol production, potentially activating protein kinase C signalling pathways. The increased levels of monogalactosyl diglyceride lipids during torpor suggest a role in neuroprotection by enhancing oligodendrocyte function and myelination. Our comprehensive lipidomic profiling provides detailed insights into lipid dynamics associated with hibernation and underscores the potential of advanced MS/MS methodologies in lipidomics for developing therapeutic strategies against neurodegenerative diseases.
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Affiliation(s)
- Carolina Gonzalez-Riano
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte 28660, España
| | - Gonzalo León-Espinosa
- Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Campus Montegancedo, Pozuelo de Alarcón, Madrid 28223, Spain; Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Madrid 28668, Spain
| | - Mamen Regalado-Reyes
- Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Campus Montegancedo, Pozuelo de Alarcón, Madrid 28223, Spain
| | - Antonia García
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte 28660, España
| | - Javier DeFelipe
- Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Campus Montegancedo, Pozuelo de Alarcón, Madrid 28223, Spain; Instituto Cajal (CSIC), Avenida Doctor Arce 37, Madrid 28002, Spain
| | - Coral Barbas
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte 28660, España.
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2
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Blanco MB, Smith DL, Greene LK, Lin J, Klopfer PH. Food deprivation is associated with telomere elongation during hibernation in a primate. Biol Lett 2025; 21:20240531. [PMID: 39933571 DOI: 10.1098/rsbl.2024.0531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 11/30/2024] [Accepted: 01/06/2025] [Indexed: 02/13/2025] Open
Abstract
Telomeres, the protective ends of chromosomes, progressively shorten due to incomplete mitotic replication and oxidative stress. In some organisms, transient telomere elongation may occur, for example, when individuals have an energy surplus to counter stress-induced life events or when elongating telomeres is a last chance to increase fitness. Mammalian hibernators are good models to test telomere dynamics, as they cycle between prolonged bouts of metabolic depression (torpor) punctuated by short surges to euthermia (arousals). We studied captive fat-tailed dwarf lemurs (Cheirogaleus medius), strepsirrhine primate hibernators, that were food-deprived (n = 8) or fed daily (n = 7) during hibernation (4.5 months). We compared telomere lengths, assayed via qPCR from oral swabs, at five strategic time points that span a full year. Food-deprived subjects underwent multi-day torpor/arousal cycles, lost considerable body mass and elongated telomeres during hibernation but shortened them upon emergence. In contrast, food-provisioned subjects ate daily, lost body mass more slowly, underwent shallower and shorter torpor bouts and experienced little change in telomere lengths during the same periods. Our results highlight a complex relationship between telomere dynamics, energy balance and torpor expression. Further investigation is warranted to elucidate the regulation of protective mechanisms in these primate hibernators.
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Affiliation(s)
- Marina B Blanco
- Duke Lemur Center, Durham, NC 27705, USA
- Department of Biology, Duke University, Durham, NC 27708, USA
| | - Dana L Smith
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA
| | - Lydia K Greene
- Duke Lemur Center, Durham, NC 27705, USA
- Department of Biology, Duke University, Durham, NC 27708, USA
| | - Jue Lin
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA
| | - Peter H Klopfer
- Department of Biology, Duke University, Durham, NC 27708, USA
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3
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Morrison SF, Cano G, Hernan SL, Chiavetta P, Tupone D. Inhibition of the hypothalamic ventromedial periventricular area activates a dynorphin pathway-dependent thermoregulatory inversion in rats. Curr Biol 2025; 35:59-76.e4. [PMID: 39626667 PMCID: PMC11706707 DOI: 10.1016/j.cub.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 09/06/2024] [Accepted: 11/05/2024] [Indexed: 01/11/2025]
Abstract
To maintain core body temperature in mammals, CNS thermoregulatory networks respond to cold exposure by increasing brown adipose tissue and shivering thermogenesis. However, in hibernation or torpor, this canonical thermoregulatory response is replaced by a new, emerging paradigm, thermoregulatory inversion (TI), an alternative homeostatic state in which cold exposure inhibits thermogenesis and warm exposure stimulates thermogenesis. Here, we demonstrate that in the non-torpid rat, either exclusion of the canonical thermoregulatory integrator in the preoptic hypothalamus or inhibition of neurons in the ventromedial periventricular area (VMPeA) induces the TI state through an alternative thermoregulatory pathway. Within this pathway, we have identified a dynorphinergic input to the dorsomedial hypothalamus from the dorsolateral parabrachial nucleus that plays a critical role in mediating the cold-evoked inhibition of thermogenesis during TI. Our results reveal a novel thermosensory reflex circuit within the mammalian CNS thermoregulatory pathways and support the potential for pharmacologically inducing the TI state to elicit therapeutic hypothermia in non-hibernating species, including humans.
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Affiliation(s)
- Shaun F Morrison
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USA
| | - Georgina Cano
- Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Shelby L Hernan
- Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Pierfrancesco Chiavetta
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USA
| | - Domenico Tupone
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USA; Department of Biomedical and Neuromotor Science, University of Bologna, Bologna 40126, Italy.
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4
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Hao Z, Han Y, Zhao Q, Zhu M, Liu X, Yang Y, An N, He D, Lefai E, Storey KB, Chang H, Xie M. Involvement of Melatonin, Oxidative Stress, and Inflammation in the Protective Mechanism of the Carotid Artery over the Torpor-Arousal Cycle of Ground Squirrels. Int J Mol Sci 2024; 25:12888. [PMID: 39684599 DOI: 10.3390/ijms252312888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Hibernating mammals experience severe hemodynamic changes over the torpor-arousal cycle, with oxygen consumption reaching peaks during the early stage of torpor to re-enter arousal. Melatonin (MT) can improve mitochondrial function and reduce oxidative stress and inflammation. However, the regulatory mechanisms of MT action on the vascular protective function of hibernators are still unclear. Morphology, hemodynamic, mitochondrial oxidative stress, and inflammatory factors of the carotid artery were assessed in ground squirrels who were sampled during summer active (SA), late torpor (LT), and interbout arousal (IBA) conditions. Changes were assessed by methods including hematoxylin and eosin staining, color Doppler ultrasound, ELISA, Western blots, and qPCR. Changes in arterial blood and serum melatonin were also measured by blood gas analyzer and ELISA, whereas mitochondrial oxidative stress and inflammation factors of primary vascular smooth muscle cells (VSMCs) were assessed by qPCR. (1) Intima-media carotid thickness, peak systolic velocity (PSV), end diastolic blood flow velocity (EDV), maximal blood flow rate (Vmax) and pulsatility index (PI) were significantly decreased in the LT group as compared with the SA group, whereas there were no difference between the SA and IBA groups. (2) PO2, oxygen saturation, hematocrit and PCO2 in the arterial blood were significantly increased, and pH was significantly decreased in the LT group as compared with the SA and IBA groups. (3) The serum melatonin concentration was significantly increased in the LT group as compared with the SA and IBA groups. (4) MT treatment significantly reduced the elevated levels of LONP1, NF-κB, NLRP3 and IL-6 mRNA expression of VSMCs under hypoxic conditions. (5) Protein expression of HSP60 and LONP1 in the carotid artery were significantly reduced in the LT and IBA groups as compared with the SA group. (6) The proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the carotid artery of the LT group as compared with the SA and IBA groups. The carotid artery experiences no oxidative stress or inflammatory response during the torpor-arousal cycle. In addition, melatonin accumulates during torpor and alleviates oxidative stress and inflammatory responses caused by hypoxia in vitro in VSMCs from ground squirrels.
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Affiliation(s)
- Ziwei Hao
- Department of Aerospace Physiology, Air Force Medical University, Xi'an 710032, China
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Yuting Han
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Qi Zhao
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Minghui Zhu
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Xiaoxuan Liu
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Yingyu Yang
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Ning An
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Dinglin He
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Etienne Lefai
- INRAE, Unité de Nutrition Humaine, Université Clermont Auvergne, UMR 1019, F-63000 Clermont-Ferrand, France
| | - Kenneth B Storey
- Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
| | - Hui Chang
- Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China
| | - Manjiang Xie
- Department of Aerospace Physiology, Air Force Medical University, Xi'an 710032, China
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5
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Salucci S, Hitrec T, Piscitiello E, Occhinegro A, Alberti L, Taddei L, Burattini S, Luppi M, Tupone D, Amici R, Faenza I, Cerri M. Multiorgan ultrastructural changes in rats induced in synthetic torpor. Front Physiol 2024; 15:1451644. [PMID: 39628940 PMCID: PMC11611833 DOI: 10.3389/fphys.2024.1451644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 10/29/2024] [Indexed: 12/06/2024] Open
Abstract
Torpor is a state used by several mammals to survive harsh winters and avoid predation, characterized by a drastic reduction in metabolic rate followed by a decrease in body temperature, heart rate, and many physiological variables. During torpor, all organs and systems must adapt to the new low-energy expenditure conditions to preserve physiological homeostasis. These adaptations may be exploited in a translational perspective in several fields. Recently, many features of torpor were shown to be mimicked in non-hibernators by the inhibition of neurons within the brainstem region of the Raphe Pallidus. The physiological resemblance of this artificial state, called synthetic torpor, with natural torpor has so far been described only in physiological terms, but no data have been shown regarding the induced morphological changes. Here, we show the first description of the ultrastructural changes in the liver, kidney, lung, skeletal muscle, and testis induced by a 6-hours inhibition of Raphe Pallidus neurons in a non-hibernating species, the rat.
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Affiliation(s)
- Sara Salucci
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Timna Hitrec
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Emiliana Piscitiello
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Alessandra Occhinegro
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Luca Alberti
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Ludovico Taddei
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Sabrina Burattini
- Department of Biomolecular Sciences, Carlo Bo Urbino University, Urbino, Italy
| | - Marco Luppi
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Domenico Tupone
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Roberto Amici
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Irene Faenza
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
| | - Matteo Cerri
- Department of Biomedical and Neuromotor Sciences – University of Bologna, Bologna, Italy
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6
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Fregin B, Hossain MF, Biedenweg D, Friedrichs V, Balkema-Buschmann A, Bokelmann M, Lehnert K, Mokbel D, Aland S, Scholz CC, Lehmann P, Otto O, Kerth G. Thermomechanical properties of bat and human red blood cells-Implications for hibernation. Proc Natl Acad Sci U S A 2024; 121:e2405169121. [PMID: 39401351 PMCID: PMC11513926 DOI: 10.1073/pnas.2405169121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 08/27/2024] [Indexed: 10/30/2024] Open
Abstract
Hibernation is a widespread and highly efficient mechanism to save energy in mammals. However, one major challenge of hibernation is maintaining blood circulation at low body temperatures, which strongly depends on the viscoelastic properties of red blood cells (RBCs). Here, we examined at physiologically relevant timescales the thermomechanical properties of hundreds of thousands of individual RBCs from the hibernating common noctule bat (Nyctalus noctula), the nonhibernating Egyptian fruit bat (Rousettus aegyptiacus), and humans (Homo sapiens). We exposed RBCs to temperatures encountered during normothermia and hibernation and found a significant increase in elasticity and viscosity with decreasing temperatures. Our data demonstrate that temperature adjustment of RBCs is mainly driven by membrane properties and not the cytosol while viscous dissipation in the membrane of both bat species exceeds the one in humans by a factor of 15. Finally, our results show that RBCs from both bat species reveal a transition to a more viscous-like state when temperature decreases. This process on a minute timescale has an effect size that is comparable with fluctuations in RBC viscoelasticity over the course of the year, implying that environmental factors, such as diets, have a lower impact on the capability of RBCs to respond to different temperatures than general physical properties of the cell membrane. In summary, our findings suggest membrane viscoelasticity as a promising target for identifying mechanisms that could be manipulated to ensure blood circulation at low body temperatures in humans, which may be one first step toward safe synthetic torpor in medicine and space flight.
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Affiliation(s)
- Bob Fregin
- Institute of Physics, University of Greifswald, Greifswald17489, Germany
- German Center for Cardiovascular Research, Partner Site Greifswald, Greifswald17489, Germany
| | - Mohammed Faruq Hossain
- Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald17489, Germany
| | - Doreen Biedenweg
- Institute of Physics, University of Greifswald, Greifswald17489, Germany
| | | | | | - Marcel Bokelmann
- Friedrich-Loeffler-Institut, Greifswald-Insel Riems17493, Germany
| | - Kristin Lehnert
- Department of Internal Medicine B, University Medicine Greifswald, Greifswald17475, Germany
| | - Dominic Mokbel
- Institute of Numerical Mathematics and Optimisation, Technical University Bergakademie Freiberg, Freiberg09599, Germany
- Center for Systems Biology Dresden, Dresden01307, Germany
| | - Sebastian Aland
- Institute of Numerical Mathematics and Optimisation, Technical University Bergakademie Freiberg, Freiberg09599, Germany
- Center for Systems Biology Dresden, Dresden01307, Germany
| | - Carsten C. Scholz
- Institute of Physiology, University Medicine Greifswald, Greifswald17489, Germany
| | - Philipp Lehmann
- Animal Physiology, Zoological Institute and Museum, University of Greifswald, Greifswald17489, Germany
| | - Oliver Otto
- Institute of Physics, University of Greifswald, Greifswald17489, Germany
- German Center for Cardiovascular Research, Partner Site Greifswald, Greifswald17489, Germany
| | - Gerald Kerth
- Applied Zoology and Nature Conservation, Zoological Institute and Museum, University of Greifswald, Greifswald17489, Germany
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7
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Amiya N, Nakano N, Tanaka C, Hibino S, Takakura R, Amano M, Yoshinaga T. Leptin gene expression in the brain is associated with the physiological onset of estivation in western sand lance Ammodytes japonicus. JOURNAL OF EXPERIMENTAL ZOOLOGY. PART A, ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY 2024; 341:913-924. [PMID: 38946665 DOI: 10.1002/jez.2850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/15/2024] [Accepted: 06/19/2024] [Indexed: 07/02/2024]
Abstract
Dormancy is an essential ecological characteristic for the survival of organisms that experience harsh environments. Although factors that initiate dormancy vary, suppression or cessation of feeding activities are common among taxa. To distinguish between extrinsic and intrinsic causes of metabolic reduction, we focused on estivation, which occurs in summer when the feeding activity is generally enhanced. Sand lances (genus Ammodytes) are a unique marine fish with a long estivation period from early summer to late autumn. In the present study, we aimed to elucidate the control mechanisms of estivation in western sand lance (A. japonicus), and firstly examined behavioral changes in 8 months including a transition between active and dormant phases. We found that swimming/feeding behavior gradually decreased from June, and completely disappeared by late August, indicating all individuals had entered estivation. Next, we focused on leptin, known as a feeding suppression hormone in various organisms, and examined leptin-A gene (AjLepA) expression in the brain that may regulate the seasonal behavioral pattern. AjLepA expression decreased after 7 days of fasting, suggesting that leptin has a function to regulate feeding in this species. The monthly expression dynamics of AjLepA during the feeding (active) and non-feeding (estivation) periods showed that the levels gradually increased with the onset of estivation and reached its peak when all the experimental fish had estivated. The present study suggests that the suppression of feeding activity by leptin causes shift in the physiological modes of A. japonicus before estivation.
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Affiliation(s)
- Noriko Amiya
- School of Marine Biosciences, Kitasato University, Kanagawa, Japan
| | - Nayu Nakano
- School of Marine Biosciences, Kitasato University, Kanagawa, Japan
| | - Chikaya Tanaka
- Department of Biology, Tokyo Medical University, Tokyo, Japan
| | - Shizuha Hibino
- School of Marine Biosciences, Kitasato University, Kanagawa, Japan
| | - Ryota Takakura
- Fisheries Technology Institute, Hyogo Prefectural Technology Center for Agriculture, Forestry and Fisheries, Hyogo, Japan
| | - Masafumi Amano
- School of Marine Biosciences, Kitasato University, Kanagawa, Japan
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8
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Hubert DL, Bentz EJ, Mason RT. Increased offspring size and reduced gestation length in an ectothermic vertebrate under a worst-case climate change scenario. J Therm Biol 2024; 125:103990. [PMID: 39426089 DOI: 10.1016/j.jtherbio.2024.103990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 09/27/2024] [Accepted: 09/29/2024] [Indexed: 10/21/2024]
Abstract
As global temperatures continue to rise, understanding the impacts of warming environments has become increasingly important. Temperature is especially relevant for ectothermic organisms which depend upon consistent and predictable annual temperature cycles for reproduction and development. However, additional research is required in this area to elucidate the potential impacts of climate change on future generations. To understand how projected increases in environmental temperatures may impact reproductive outcomes within natural populations of ectothermic vertebrates, we manipulated minimum ambient temperatures during gestation in Red-sided garter snakes (Thamnophis sirtalis parietalis). Wild snakes were collected in the Interlake region of Manitoba, Canada during their spring mating season and allowed to mate in controlled conditions. For the duration of gestation, mated females were placed into one of two ambient thermal conditions: temperatures emulating those found in the species' natural habitat or temperatures with a consistent 5 °C increase to match end-of-century climate change projections. We recorded observations for each litter and all neonates resulting from controlled mating trials. We observed no difference in litter sizes or birth rates between thermal conditions. However, we observed a significant reduction in gestation length and significant increase to neonate body mass and body condition associated with increased ambient temperatures. These results suggest that increased minimum temperatures during gestation may confer reproductive benefits for the northern populations of this species even under the most extreme current modeled warming predictions. We discuss the broader implications of this effect, including possible negative ecological outcomes.
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Affiliation(s)
- David L Hubert
- Department of Integrative Biology, Oregon State University, Corvallis, OR, 97333, USA.
| | - Ehren J Bentz
- Department of Psychology, Cornell University, Ithaca, NY, USA
| | - Robert T Mason
- Department of Integrative Biology, Oregon State University, Corvallis, OR, 97333, USA
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9
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Sone M, Mitsuhashi N, Sugiura Y, Matsuoka Y, Maeda R, Yamauchi A, Okahashi R, Yamashita J, Sone K, Enju S, Anegawa D, Yamaguchi Y. Identification of genes supporting cold resistance of mammalian cells: lessons from a hibernator. Cell Death Dis 2024; 15:685. [PMID: 39300059 DOI: 10.1038/s41419-024-07059-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 09/03/2024] [Accepted: 09/05/2024] [Indexed: 09/22/2024]
Abstract
Susceptibility of human cells to cold stress restricts the use of therapeutic hypothermia and long-term preservation of organs at low temperatures. In contrast, cells of mammalian hibernators possess remarkable cold resistance, but little is known about the molecular mechanisms underlying this phenomenon. In this study, we conducted a gain-of-function screening of genes that confer cold resistance to cold-vulnerable human cells using a cDNA library constructed from the Syrian hamster, a mammalian hibernator, and identified Gpx4 as a potent suppressor of cold-induced cell death. Additionally, genetic deletion of or pharmacological inhibition of Gpx4 revealed that Gpx4 is necessary for suppressing lipid peroxidation specifically under cold in hamster cell lines. Genetic disruption of other ferroptosis-suppressing pathways, namely biopterin synthesis and mitochondrial or plasma membrane CoQ reduction pathways, also accelerated cold-induced cell death under Gpx4 dysfunction. Collectively, ferroptosis-suppressing pathways protect the cells of a mammalian hibernator from cold-induced cell death and the augmentation of these pathways renders cold resistance to cells of non-hibernators, including humans.
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Grants
- 20H05766 Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- 20H05765 Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- 20B303 Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- 18K19321 Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- 23H04940 Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- 22K19320 Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- 23gm6310019 Japan Agency for Medical Research and Development (AMED)
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Affiliation(s)
- Masamitsu Sone
- Graduate School of Environmental Sciences, Hokkaido University, Sapporo, Japan.
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan.
| | - Nonoka Mitsuhashi
- Graduate School of Environmental Sciences, Hokkaido University, Sapporo, Japan
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan
| | - Yuki Sugiura
- Multiomics Platform, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University School of Medicine, Tokyo, Japan
| | - Yuta Matsuoka
- Multiomics Platform, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Rae Maeda
- Multiomics Platform, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Akari Yamauchi
- Graduate School of Environmental Sciences, Hokkaido University, Sapporo, Japan
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan
| | - Ryoto Okahashi
- Graduate School of Environmental Sciences, Hokkaido University, Sapporo, Japan
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan
| | - Junpei Yamashita
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan
| | - Kanako Sone
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan
| | - Sachiyo Enju
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan
| | - Daisuke Anegawa
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan
| | - Yoshifumi Yamaguchi
- Graduate School of Environmental Sciences, Hokkaido University, Sapporo, Japan.
- Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan.
- Inamori Research Institute for Science, Kyoto, Japan.
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10
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Gao P, Shen W, Bo T. The interaction between gut microbiota and hibernation in mammals. Front Microbiol 2024; 15:1433675. [PMID: 39323884 PMCID: PMC11423207 DOI: 10.3389/fmicb.2024.1433675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 08/30/2024] [Indexed: 09/27/2024] Open
Abstract
Hibernation, an evolved survival trait among animals, enables them to endure frigid temperatures and food scarcity during the winter months, and it is a widespread phenomenon observed in mammals. The gut microbiota, a crucial component of animal nutrition and health, exhibits particularly dynamic interactions in hibernating mammals. This manuscript comprehensively evaluates the impacts of fasting, hypothermia, and hypometabolism on the gut microbiota of hibernating mammals. It suggests that alterations in the gut microbiota may contribute significantly to the maintenance of energy metabolism and intestinal immune function during hibernation, mediated by their metabolites. By delving into these intricacies, we can gain a deeper understanding of how hibernating mammals adapt to their environments and the consequences of dietary modifications on the symbiotic relationship between the gut microbiota and the host. Additionally, this knowledge can inform our comprehension of the protective mechanisms underlying long-term fasting in non-hibernating species, including humans, providing valuable insights into nutritional strategies and health maintenance.
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Affiliation(s)
| | | | - Tingbei Bo
- School of Grassland Science, Beijing Forestry University, Beijing, China
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11
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Nagashima S, Yamaguchi ST, Zhou Z, Norimoto H. Transient Cooling Resets Circadian Rhythms of Locomotor Activity in Lizards. J Biol Rhythms 2024:7487304241273190. [PMID: 39257103 DOI: 10.1177/07487304241273190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/12/2024]
Abstract
Animals frequently experience temperature fluctuations in their natural life cycle, including periods of low temperatures below their activity range. For example, poikilothermic animals are known to enter a hibernation-like state called brumation during transient cooling. However, the knowledge regarding the physiological responses of brumation is limited. Specifically, the impact of exposure to low-temperature conditions outside the range of temperature compensation on the subsequent circadian behavioral rhythms remains unclear. In this study, we investigated the effects of transient cooling on the behavioral circadian rhythm in the non-avian reptile, the bearded dragon (Pogona vitticeps). Under constant light (LL) conditions at 30 °C, the animals exhibited a free-running rhythm, and exposure to low temperatures (4 °C) caused a complete cessation of locomotion. Furthermore, we revealed that the behavioral rhythm after rewarming is determined not by the circadian phase at the onset or the duration of cooling, but by the timing of cooling cessation.
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Affiliation(s)
- Sakimi Nagashima
- Graduate School of Science, Nagoya University, Nagoya, Japan
- Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Sho T Yamaguchi
- Graduate School of Science, Nagoya University, Nagoya, Japan
- Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Zhiwen Zhou
- Graduate School of Science, Nagoya University, Nagoya, Japan
- Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Hiroaki Norimoto
- Graduate School of Science, Nagoya University, Nagoya, Japan
- Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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12
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Wang X, Chen S, Wang X, Song Z, Wang Z, Niu X, Chen X, Chen X. Application of artificial hibernation technology in acute brain injury. Neural Regen Res 2024; 19:1940-1946. [PMID: 38227519 DOI: 10.4103/1673-5374.390968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 10/20/2023] [Indexed: 01/17/2024] Open
Abstract
Controlling intracranial pressure, nerve cell regeneration, and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury. There is currently a lack of effective treatment methods. Hibernation has the characteristics of low temperature, low metabolism, and hibernation rhythm, as well as protective effects on the nervous, cardiovascular, and motor systems. Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body's metabolism, lowering the body's core temperature, and allowing the body to enter a state similar to hibernation. This review introduces artificial hibernation technology, including mild hypothermia treatment technology, central nervous system regulation technology, and artificial hibernation-inducer technology. Upon summarizing the relevant research on artificial hibernation technology in acute brain injury, the research results show that artificial hibernation technology has neuroprotective, anti-inflammatory, and oxidative stress-resistance effects, indicating that it has therapeutic significance in acute brain injury. Furthermore, artificial hibernation technology can alleviate the damage of ischemic stroke, traumatic brain injury, cerebral hemorrhage, cerebral infarction, and other diseases, providing new strategies for treating acute brain injury. However, artificial hibernation technology is currently in its infancy and has some complications, such as electrolyte imbalance and coagulation disorders, which limit its use. Further research is needed for its clinical application.
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Affiliation(s)
- Xiaoni Wang
- Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shulian Chen
- Characteristic Medical Center of People's Armed Police Forces, Tianjin, China
| | - Xiaoyu Wang
- Characteristic Medical Center of People's Armed Police Forces, Tianjin, China
| | - Zhen Song
- Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ziqi Wang
- Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaofei Niu
- Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaochu Chen
- Characteristic Medical Center of People's Armed Police Forces, Tianjin, China
| | - Xuyi Chen
- Characteristic Medical Center of People's Armed Police Forces, Tianjin, China
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13
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Lammert TL, Müller J, Ferreira SC, Teubenbacher U, Cornils JS, Stalder G, Painer-Gigler J, Ruf T, Bieber C, Pohlin F. No negative effects of intra-abdominal bio-logger implantation under general anaesthesia on spatial cognition learning in a hibernator the edible dormouse. PLoS One 2024; 19:e0307551. [PMID: 39197002 PMCID: PMC11356448 DOI: 10.1371/journal.pone.0307551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 07/09/2024] [Indexed: 08/30/2024] Open
Abstract
The effect of hibernation on cognitive capacities of individuals is not fully understood, as studies provide conflicting results. Most studies focus on behavioural observations without taking the physiological state of individuals to account. To mechanistically understand the effect of hibernation on the brain, physiological parameters need to be included. The implantation of bio-loggers can provide insights on i.e. body temperature without further manipulation of the animals. Surgeries and anaesthesia, however, can harm animals' health and cause cognitive dysfunction, potentially biasing data collected through bio-loggers. We investigated the effects of bio-logger implantation surgery on cognitive performance and learning, controlling for animal and study design characteristics. First, juvenile dormice successfully learned to solve a spatial cognition task using a vertical maze. Distance, transitions, velocity, and duration were measured as indicators for performance. After training, bio-loggers were implanted intra-abdominally under general anaesthesia. Animals were re-tested in the maze two weeks after. We found no effect of bio-logger implantation and surgery on performance. This study is the first to show spatial cognition learning in edible dormice and provides a full description of the peri-anaesthetic management and a protocol for bio-logger implantation surgery in dormice. Importantly, measures were taken to mitigate common anaesthetic complications that could lead to post-operative cognitive dysfunction and influence animal behaviour. By pairing physiological measurements through bio-logger implantation with behaviour and cognition measurements, future research will significantly advance the understanding on mechanisms of learning and behaviour.
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Affiliation(s)
- Tabea Loreen Lammert
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Jan Müller
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
| | | | - Ursula Teubenbacher
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Jessica Svea Cornils
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Gabrielle Stalder
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Johanna Painer-Gigler
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Thomas Ruf
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Claudia Bieber
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Friederike Pohlin
- Department of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria
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14
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Dori P, Anastasio I, Macchi E, Manenti I, Hones M, Carosi M. Hibernating or not hibernating? Brown bears' response to a mismatch between environmental natural cues and captive management, and its welfare implications. PLoS One 2024; 19:e0306537. [PMID: 39083476 PMCID: PMC11290645 DOI: 10.1371/journal.pone.0306537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 06/19/2024] [Indexed: 08/02/2024] Open
Abstract
In wild brown bears, likely factors triggering hibernation response to harsh environmental conditions are temperature, photoperiod, and food resources availability. In fact, constantly fed captive brown bears are described as skipping hibernation being active all year-round. Is the hibernation response so flexible and subordinate to contingencies, or else is an adaptation that, if dismissed, may negatively impact on bear well-being? This study investigates the potential hibernation response in captive brown bears under unvaried management conditions using an integrative approach simultaneously analyzing multiple animal-based variables together with environmental covariates. Data from a mid-latitude zoo revealed distinct behavioral, fecal glucocorticoids, and body condition score seasonal fluctuations, resembling natural hibernation cycles, despite constant food access. Environmental variables like photoperiod and visitor numbers significantly influenced activity levels. Bears exhibited behaviors indicative of hyperphagia and fall transition, such as appetitive feeding and denning behaviors. Hormonal analyses revealed high fecal cortisol metabolites levels during hyperphagia, suggesting physiological responses to seasonal changes. Findings underscore the importance of environmental cues and food availability in shaping zoo bear behavior and physiology. Considering that the hibernating vs. non-hibernating description might represent an oversimplification, management strategies should deal with captive bear potential need to freely express their adaptive predispositions by accommodating their natural behaviors, such as providing denning spots and adjusting diet composition as soon as typical hyperphagic and predenning behaviors emerge, ultimately enhancing their well-being.
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Affiliation(s)
- Paolo Dori
- Department of Science, Roma Tre University, Rome, Italy
| | | | | | - Isabella Manenti
- Department of Veterinary Science, University of Turin, Turin, Italy
| | | | - Monica Carosi
- Department of Science, Roma Tre University, Rome, Italy
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15
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Redon L, Constant T, Smith S, Habold C, Giroud S. Understanding seasonal telomere length dynamics in hibernating species. J Therm Biol 2024; 123:103913. [PMID: 39002254 DOI: 10.1016/j.jtherbio.2024.103913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 06/26/2024] [Accepted: 06/27/2024] [Indexed: 07/15/2024]
Abstract
Oxidative stress is thought to be one of the main causes of ageing as it progressively damages cell components throughout life, eventually causing cellular failure and apoptosis. In many organisms, telomeres shorten throughout life under the effect of, amongst other factors, oxidative stress, and are therefore commonly used as marker of biological ageing. However, hibernators, which are regularly exposed to acute oxidative stress when rewarming from torpor, are unexpectedly long-lived. In this review, we explore the causes of oxidative stress associated with hibernation and its impact on telomere dynamics in different taxa, focussing on hibernating rodents. We then speculate on the adaptive mechanisms of hibernators to compensate for the effects of oxidative stress, which may explain their increased longevity. Because winter hibernation appears to be associated with high oxidative stress, hibernators, particularly rodents, may periodically invest in repair mechanisms and antioxidant defences, resulting in seasonal variations in telomere lengths. This research shows how species with a slow life-history strategy deal with large changes in oxidative stress, unifying evolutionary and physiological theories of ageing. Because of the marked seasonal variation in telomere length, we also draw attention when using telomeres as markers for biological aging in seasonal heterotherms and possibly in other highly seasonal species.
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Affiliation(s)
- Lilian Redon
- Research Institute of Wildlife Ecology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine Vienna, Austria.
| | - Théo Constant
- Department of Ecology Physiology Ethology, Pluridisciplinary Institute Hubert Curien, UMR 7179 CNRS/UdS, Strasbourg, France
| | - Steve Smith
- Konrad Lorenz Institute of Ethology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine Vienna, Austria
| | - Caroline Habold
- Department of Ecology Physiology Ethology, Pluridisciplinary Institute Hubert Curien, UMR 7179 CNRS/UdS, Strasbourg, France
| | - Sylvain Giroud
- Research Institute of Wildlife Ecology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine Vienna, Austria.
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16
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Findlay-Robinson R, Hill DL. Hibernation nest site selection but not overwinter activity is associated with microclimatic conditions in a hibernating mammal. J Therm Biol 2024; 123:103909. [PMID: 39084175 DOI: 10.1016/j.jtherbio.2024.103909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 06/30/2024] [Accepted: 07/02/2024] [Indexed: 08/02/2024]
Abstract
Fine-scale variation in microclimates between habitats may impact energy consumption for the organisms that inhabit them. This may be particularly important for sedentary species or those unable to change habitats for long periods, such as hibernators. Low ambient temperatures were traditionally thought key to microclimatic selection for hibernation locations, but recent research suggests that other factors may contribute or exceed ambient temperature in importance. We aimed to characterise microclimates at hibernacula of wild hibernating hazel dormice Muscardinus avellanarius, and test how these microclimates differ to those at locations without hibernacula using a microclimatic modelling approach. Dormice hibernated in areas with warmer soil temperatures and lower variability in humidity and relative shortwave radiation. These results add to the growing body of evidence that low ambient temperatures may not be the primary driver of hibernation microclimate selection, although temperature is still likely to play an important role. We also found that ambient temperatures measured at the microclimatic level were substantially buffered compared to point samples taken at the nearest weather station (∼1.6 km away), highlighting the importance of considering microclimates in wildlife conservation in the face of future environmental change.
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Affiliation(s)
- Rachel Findlay-Robinson
- Institute of Science and Environment, University of Cumbria, Ambleside, Cumbria, LA22 9BB, UK.
| | - Davina L Hill
- School of Biodiversity, One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK; School of Animal, Plant and Environmental Sciences, University of the Witwatersrand, Johannesburg, Private Bag 3, Wits 2050, South Africa.
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17
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Ferris E, Gonzalez Murcia JD, Cristina Rodriguez A, Steinwand S, Stacher Hörndli C, Traenkner D, Maldonado-Catala PJ, Gregg C. Genomic Convergence in Hibernating Mammals Elucidates the Genetics of Metabolic Regulation in the Hypothalamus. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.26.600891. [PMID: 38979381 PMCID: PMC11230405 DOI: 10.1101/2024.06.26.600891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Abstract
Elucidating the genetic basis of mammalian metabolism could help define mechanisms central to health and disease. Here, we define conserved cis-regulatory elements (CREs) and programs for mammalian metabolic control. We delineate gene expression and chromatin responses in the mouse hypothalamus for 7 steps of the Fed-to-Fasted-to-Refed (FFR) response process. Comparative genomics of hibernating versus non-hibernating lineages then illuminates cis-elements showing convergent changes in hibernators. Hibernators accumulated loss-of-function effects for specific CREs regulating hypothalamic FFR responses. Multi-omics approaches pinpoint key CREs, genes, regulatory programs, and cell types in the divergence of hibernating and homeothermic lineages. The refeeding period after extended fasting is revealed as one critical period of chromatin remodeling with convergent genomic changes. This genetic framework is a step toward harnessing hibernator adaptations in medicine.
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Affiliation(s)
- Elliott Ferris
- Departments of Neurobiology, University of Utah; Salt Lake City, 84105, USA
| | | | | | - Susan Steinwand
- Departments of Neurobiology, University of Utah; Salt Lake City, 84105, USA
| | | | - Dimitri Traenkner
- Departments of Neurobiology, University of Utah; Salt Lake City, 84105, USA
| | - Pablo J Maldonado-Catala
- Departments of Neurobiology, University of Utah; Salt Lake City, 84105, USA
- Biomedical Informatics, University of Utah; Salt Lake City, 84105, USA
| | - Christopher Gregg
- Departments of Neurobiology, University of Utah; Salt Lake City, 84105, USA
- Human Genetics, University of Utah; Salt Lake City, 84105, USA
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18
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Steinwand S, Stacher Hörndli C, Ferris E, Emery J, Gonzalez Murcia JD, Cristina Rodriguez A, Leydsman TC, Chaix A, Thomas A, Davey C, Gregg C. Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.26.600851. [PMID: 38979203 PMCID: PMC11230392 DOI: 10.1101/2024.06.26.600851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Abstract
Our study elucidates functional roles for conserved cis-elements associated with the evolution of mammalian hibernation. Genomic analyses found topologically associated domains (TADs) that disproportionately accumulated convergent genomic changes in hibernators, including the TAD for the Fat Mass & Obesity (Fto) locus. Some hibernation-linked cis-elements in this TAD form regulatory contacts with multiple neighboring genes. Knockout mice for these cis-elements exhibit Fto, Irx3, and Irx5 gene expression changes, impacting hundreds of genes downstream. Profiles of pre-torpor, torpor, and post-torpor phenotypes found distinct roles for each cis-element in metabolic control, while a high caloric diet uncovered different obesogenic effects. One cis-element promoting a lean phenotype influences foraging behaviors throughout life, affecting specific behavioral sequences. Thus, convergent evolution in hibernators pinpoints functional genetic mechanisms of mammalian metabolic control.
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Affiliation(s)
- Susan Steinwand
- Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA
| | | | - Elliott Ferris
- Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA
| | - Jared Emery
- Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA
| | | | | | - Tyler C. Leydsman
- Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA
| | - Amandine Chaix
- Department of Nutrition and Integrative Physiology, University of Utah; Salt Lake City, 84105, USA
| | - Alun Thomas
- Division of Epidemiology, University of Utah; Salt Lake City, 84105, USA
- Study Design and Biostatistics Center, University of Utah; Salt Lake City, 84105, USA
| | - Crystal Davey
- Mutation Generation & Detection Core Facility, University of Utah; Salt Lake City, 84105, USA
| | - Christopher Gregg
- Department of Neurobiology, University of Utah; Salt Lake City, 84105, USA
- Department of Human Genetics, University of Utah; Salt Lake City, 84105, USA
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19
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Ai X, Lin R, Ali Z, Zhu Q, Ding L, Shi H, Hong M. Seasonal changes in hepatic lipid metabolism and apoptosis in Chinese soft-shelled turtle (Pelodiscus sinensis). Comp Biochem Physiol C Toxicol Pharmacol 2024; 280:109883. [PMID: 38437998 DOI: 10.1016/j.cbpc.2024.109883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 01/22/2024] [Accepted: 02/29/2024] [Indexed: 03/06/2024]
Abstract
Chinese soft-shelled turtle (Pelodiscus sinensis) hibernates without eating and drinking when the ambient temperature is very low. To better understand the characteristics of energy utilization during hibernation, the turtles in the physiological phases of summer active (SA), Pre-Hibernation (Pre-H), Mid-Hibernation (Mid-H) and early arousal (EA) were sampled. The results showed that the levels of serum triglyceride and hepatic lipid droplet were markedly increased in Pre-H and decreased in Mid-H compared with that in SA, indicating that P. sinensis experiences lipid accumulation in Pre-H and lipid is the predominant energy reserve during hibernation. The mRNA expression levels of genes (FABP and CPT-2) involved in lipolysis and lipid oxidation were up-regulated in Mid-H, while the genes related to lipid synthesis (FAS, ACSL-1, ACC, elovl5, and SCD1) were inhibited in Mid-H. Meanwhile, the mRNA expression levels of endoplasmic reticulum stress marker gene Bip and key genes (ATF4, ATF6, and IRE1α) involving the unfolded protein response were significantly increased in Mid-H and EA. Also, the expression levels of genes (ASK1, JNK1, and Bax) associated with cell apoptosis increased in Mid-H and EA, however, the expression of Bcl2 was inhibited in Mid-H. Therefore, hibernation can cause endoplasmic reticulum stress and apoptosis. The findings will provide a theoretical framework for an animal's cold adaptation and offer insights into preventing and managing metabolic syndrome.
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Affiliation(s)
- Xiaoqi Ai
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, Hainan, China
| | - Rui Lin
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, Hainan, China
| | - Zeeshan Ali
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, Hainan, China
| | - Qingjun Zhu
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, Hainan, China
| | - Li Ding
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, Hainan, China.
| | - Haitao Shi
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, Hainan, China
| | - Meiling Hong
- Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou, Hainan, China.
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20
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Nakayama D, Makino T. Convergent accelerated evolution of mammal-specific conserved non-coding elements in hibernators. Sci Rep 2024; 14:11754. [PMID: 38782990 PMCID: PMC11116591 DOI: 10.1038/s41598-024-62455-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 05/16/2024] [Indexed: 05/25/2024] Open
Abstract
Mammals maintain their body temperature, yet hibernators can temporarily lower their metabolic rate as an energy-saving strategy. It has been proposed that hibernators evolved independently from homeotherms, and it is possible that the convergent evolution of hibernation involved common genomic changes among hibernator-lineages. Since hibernation is a seasonal trait, the evolution of gene regulatory regions in response to changes in season may have been important for the acquisition of hibernation traits. High-frequency accumulation of mutations in conserved non-coding elements (CNEs) could, in principle, alter the expression of neighboring genes and thereby contribute to the acquisition of new traits. To address this possibility, we performed a comparative genomic analysis of mammals to identify accelerated CNEs commonly associated with hibernation. We found that accelerated CNEs are common to hibernator-lineages and could be involved with hibernation. We also found that common factors of genes that located near accelerated CNEs and are differentially expressed between normal and hibernation periods related to gene regulation and cell-fate determination. It suggests that the molecular mechanisms controlling hibernation have undergone convergent evolution. These results help broaden our understanding of the genetic adaptations that facilitated hibernation in mammals and may offer insights pertaining to stress responses and energy conservation.
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Affiliation(s)
- Daiki Nakayama
- Department of Biology, Faculty of Science, Tohoku University, 6-3, Aramaki Aza Aoba, Aoba-Ku, Sendai, 980-8578, Japan
| | - Takashi Makino
- Department of Biology, Faculty of Science, Tohoku University, 6-3, Aramaki Aza Aoba, Aoba-Ku, Sendai, 980-8578, Japan.
- Graduate School of Life Sciences, Tohoku University, 6-3, Aramaki Aza Aoba, Aoba-Ku, Sendai, 980-8578, Japan.
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21
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Lewis CTA, Melhedegaard EG, Ognjanovic MM, Olsen MS, Laitila J, Seaborne RAE, Gronset M, Zhang C, Iwamoto H, Hessel AL, Kuehn MN, Merino C, Amigo N, Frobert O, Giroud S, Staples JF, Goropashnaya AV, Fedorov VB, Barnes B, Toien O, Drew K, Sprenger RJ, Ochala J. Remodeling of skeletal muscle myosin metabolic states in hibernating mammals. eLife 2024; 13:RP94616. [PMID: 38752835 PMCID: PMC11098559 DOI: 10.7554/elife.94616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2024] Open
Abstract
Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20 °C). Upon repeating loaded Mant-ATP chase experiments at 8 °C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.
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Affiliation(s)
| | | | - Marija M Ognjanovic
- Department of Biomedical Sciences, University of CopenhagenCopenhagenDenmark
| | - Mathilde S Olsen
- Department of Biomedical Sciences, University of CopenhagenCopenhagenDenmark
| | - Jenni Laitila
- Department of Biomedical Sciences, University of CopenhagenCopenhagenDenmark
| | - Robert AE Seaborne
- Department of Biomedical Sciences, University of CopenhagenCopenhagenDenmark
- Centre for Human and Applied Physiological Sciences, Faculty of Life Sciences & Medicine, King’s College LondonLondonUnited Kingdom
| | - Magnus Gronset
- Department of Cellular and Molecular Medicine, University of CopenhagenCopenhagenDenmark
| | - Changxin Zhang
- Department of Computational Medicine and Bioinformatics, University of MichiganAnn ArborUnited States
| | - Hiroyuki Iwamoto
- Spring-8, Japan Synchrotron Radiation Research InstituteHyogoJapan
| | - Anthony L Hessel
- Institute of Physiology II, University of MuensterMuensterGermany
- Accelerated Muscle Biotechnologies ConsultantsBostonUnited States
| | - Michel N Kuehn
- Institute of Physiology II, University of MuensterMuensterGermany
- Accelerated Muscle Biotechnologies ConsultantsBostonUnited States
| | | | | | - Ole Frobert
- Department of Clinical Medicine, Faculty of Health, Aarhus UniversityAarhusDenmark
- Faculty of Health, Department of Cardiology, Örebro UniversityÖrebroSweden
| | - Sylvain Giroud
- Energetics Lab, Department of Biology, Northern Michigan UniversityMarquetteUnited States
- Research Institute of Wildlife Ecology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine ViennaViennaAustria
| | - James F Staples
- Department of Biology, University of Western OntarioLondonCanada
| | - Anna V Goropashnaya
- Center for Transformative Research in Metabolism, Institute of Arctic Biology, University of Alaska FairbanksFairbanksUnited States
| | - Vadim B Fedorov
- Center for Transformative Research in Metabolism, Institute of Arctic Biology, University of Alaska FairbanksFairbanksUnited States
| | - Brian Barnes
- Center for Transformative Research in Metabolism, Institute of Arctic Biology, University of Alaska FairbanksFairbanksUnited States
| | - Oivind Toien
- Center for Transformative Research in Metabolism, Institute of Arctic Biology, University of Alaska FairbanksFairbanksUnited States
| | - Kelly Drew
- Center for Transformative Research in Metabolism, Institute of Arctic Biology, University of Alaska FairbanksFairbanksUnited States
| | - Ryan J Sprenger
- Department of Zoology, University of British ColumbiaVancouverCanada
| | - Julien Ochala
- Department of Biomedical Sciences, University of CopenhagenCopenhagenDenmark
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22
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Blanco MB, Smith DL, Greene LK, Yoder AD, Ehmke EE, Lin J, Klopfer PH. Telomere dynamics during hibernation in a tropical primate. J Comp Physiol B 2024; 194:213-219. [PMID: 38466418 DOI: 10.1007/s00360-024-01541-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 01/13/2024] [Accepted: 01/23/2024] [Indexed: 03/13/2024]
Abstract
Hibernation is a widespread metabolic strategy among mammals for surviving periods of food scarcity. During hibernation, animals naturally alternate between metabolically depressed torpor bouts and energetically expensive arousals without ill effects. As a result, hibernators are promising models for investigating mechanisms that buffer against cellular stress, including telomere protection and restoration. In non-hibernators, telomeres, the protective structural ends of chromosomes, shorten with age and metabolic stress. In temperate hibernators, however, telomere shortening and elongation can occur in response to changing environmental conditions and associated metabolic state. We investigate telomere dynamics in a tropical hibernating primate, the fat-tailed dwarf lemur (Cheirogaleus medius). In captivity, these lemurs can hibernate when maintained under cold temperatures (11-15 °C) with limited food provisioning. We study telomere dynamics in eight fat-tailed dwarf lemurs at the Duke Lemur Center, USA, from samples collected before, during, and after the hibernation season and assayed via qPCR. Contrary to our predictions, we found that telomeres were maintained or even lengthened during hibernation, but shortened immediately thereafter. During hibernation, telomere lengthening was negatively correlated with time in euthermia. Although preliminary in scope, our findings suggest that there may be a preemptive, compensatory mechanism to maintain telomere integrity in dwarf lemurs during hibernation. Nevertheless, telomere shortening immediately afterward may broadly result in similar outcomes across seasons. Future studies could profitably investigate the mechanisms that offset telomere shortening within and outside of the hibernation season and whether those mechanisms are modulated by energy surplus or crises.
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Affiliation(s)
- M B Blanco
- Duke Lemur Center, Durham, NC, 27705, USA.
- Department of Biology, Duke University, Durham, NC, 27708, USA.
| | - D L Smith
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA, 94143, USA
| | - L K Greene
- Duke Lemur Center, Durham, NC, 27705, USA
- Department of Biology, Duke University, Durham, NC, 27708, USA
| | - A D Yoder
- Department of Biology, Duke University, Durham, NC, 27708, USA
| | - E E Ehmke
- Duke Lemur Center, Durham, NC, 27705, USA
| | - J Lin
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA, 94143, USA
| | - P H Klopfer
- Department of Biology, Duke University, Durham, NC, 27708, USA
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23
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Guo S, Yang W, Chen D, Ren B, Guo L, Wang X, Xie W, Fan S, Artigas Ramirez MD, Han Y, Yuan Z, Zhang H, Weng Q. The effects of low ambient temperature on steroidogenesis and mitochondrial functions in the testes of wild ground squirrels (Spermophilus dauricus). Comp Biochem Physiol A Mol Integr Physiol 2024; 290:111585. [PMID: 38228267 DOI: 10.1016/j.cbpa.2024.111585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 01/11/2024] [Accepted: 01/12/2024] [Indexed: 01/18/2024]
Abstract
Seasonal reproduction is a widely used breeding strategy in wildlife, especially vertebrates inhabiting temperate regions. Generally, ambient temperature is considered a significant factor influencing the reproductive status of animals. In the present study, wild ground squirrels (Spermophilus dauricus), typical seasonal breeders, were used as an animal model to investigate the mechanism behind the impact of low ambient temperature on testicular function. To simulate the winter environment of wild ground squirrels, we lowered the temperature gradient in the rearing environment to 4 °C. At sampling, the body surface temperature of the squirrels reared under normal ambient temperature (22 °C, NAT group) and the low ambient temperature (4 °C, LAT group) were 31.5 °C and 22.8 °C, respectively. Subsequently, we conducted immunohistochemical assays, qPCR, and enzyme-linked immunosorbent assays (ELISA) to examine the variations in testicular functions, as well as the dynamics and functions of mitochondria, in the squirrels of NAT and LAT groups. As a result, the levels of positive immunostaining for PCNA, P21, and P27 were significantly lower in the testes of LAT group, while the levels of immunostaining for Cleaved Caspase-3 and TUNEL were significantly higher. In addition, the low-temperature treatment reduced the expression level of steroidogenesis-related genes, including LHR, FSHR, GATA-4, P450scc, and P450arom, and decreased the testosterone concentration. Moreover, markers of mitochondrial fission and fusion, DRP1 and MFN2, respectively, were increased in the testes of LAT group. Additionally, the mRNA level of SOD1 was notably higher in the testes of LAT group. In conclusion, the low ambient temperature inhibited spermatogenesis, steroidogenesis, as well as mitochondrial dynamics and functions in the testes of wild ground squirrels.
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Affiliation(s)
- Shiman Guo
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Wenjin Yang
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Di Chen
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Baolong Ren
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Li Guo
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Xi Wang
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Wenqian Xie
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Sijie Fan
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Maria Daniela Artigas Ramirez
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Yingying Han
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Zhengrong Yuan
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Haolin Zhang
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.
| | - Qiang Weng
- Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.
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24
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Lewis CTA, Melhedegaard EG, Ognjanovic MM, Olsen MS, Laitila J, Seaborne RAE, Gronset MN, Zhang C, Iwamoto H, Hessel AL, Kuehn MN, Merino C, Amigo N, Frobert O, Giroud S, Staples JF, Goropashnaya AV, Fedorov VB, Barnes BM, Toien O, Drew KL, Sprenger RJ, Ochala J. Remodelling of Skeletal Muscle Myosin Metabolic States in Hibernating Mammals. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.11.14.566992. [PMID: 38014200 PMCID: PMC10680686 DOI: 10.1101/2023.11.14.566992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20°C). Upon repeating loaded Mant-ATP chase experiments at 8°C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.
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25
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Ding SS, Fox JL, Gordus A, Joshi A, Liao JC, Scholz M. Fantastic beasts and how to study them: rethinking experimental animal behavior. J Exp Biol 2024; 227:jeb247003. [PMID: 38372042 PMCID: PMC10911175 DOI: 10.1242/jeb.247003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2024]
Abstract
Humans have been trying to understand animal behavior at least since recorded history. Recent rapid development of new technologies has allowed us to make significant progress in understanding the physiological and molecular mechanisms underlying behavior, a key goal of neuroethology. However, there is a tradeoff when studying animal behavior and its underlying biological mechanisms: common behavior protocols in the laboratory are designed to be replicable and controlled, but they often fail to encompass the variability and breadth of natural behavior. This Commentary proposes a framework of 10 key questions that aim to guide researchers in incorporating a rich natural context into their experimental design or in choosing a new animal study system. The 10 questions cover overarching experimental considerations that can provide a template for interspecies comparisons, enable us to develop studies in new model organisms and unlock new experiments in our quest to understand behavior.
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Affiliation(s)
- Siyu Serena Ding
- Max Planck Institute of Animal Behavior, 78464 Konstanz, Germany
- Centre for the Advanced Study of Collective Behaviour, University of Konstanz, 78464 Konstanz, Germany
| | - Jessica L. Fox
- Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Andrew Gordus
- Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Abhilasha Joshi
- Departments of Physiology and Psychiatry, University of California, San Francisco, CA 94158, USA
| | - James C. Liao
- Department of Biology, The Whitney Laboratory for Marine Bioscience, University of Florida, St. Augustine, FL 32080, USA
| | - Monika Scholz
- Max Planck Research Group Neural Information Flow, Max Planck Institute for Neurobiology of Behavior – caesar, 53175 Bonn, Germany
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26
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Allison AZT, Conway CJ, Morris AE, Goldberg AR, Lohr K, Richards R, Almack JA. Hit Snooze: An Imperiled Hibernator Assesses Spring Snow Conditions to Decide Whether to Terminate Hibernation or Reenter Torpor. ECOLOGICAL AND EVOLUTIONARY PHYSIOLOGY 2024; 97:53-63. [PMID: 38717368 DOI: 10.1086/729775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2024]
Abstract
AbstractMany animals follow annual cycles wherein physiology and behavior change seasonally. Hibernating mammals undergo one of the most drastic seasonal alterations of physiology and behavior, the timing of which can have significant fitness consequences. The environmental cues regulating these profound phenotypic changes will heavily influence whether hibernators acclimate and ultimately adapt to climate change. Hence, identifying the cues and proximate mechanisms responsible for hibernation termination timing is critical. Northern Idaho ground squirrels (Urocitellus brunneus)-a rare, endemic species threatened with extinction-exhibit substantial variation in hibernation termination phenology, but it is unclear what causes this variation. We attached geolocators to free-ranging squirrels to test the hypothesis that squirrels assess surface conditions in spring before deciding whether to terminate seasonal heterothermy or reenter torpor. Northern Idaho ground squirrels frequently reentered torpor following a brief initial emergence from hibernacula and were more likely to do so earlier in spring or when challenged by residual snowpack. Female squirrels reentered torpor when confronted with relatively shallow snowpack upon emergence, whereas male squirrels reentered torpor in response to deeper spring snowpack. This novel behavior was previously assumed to be physiologically constrained in male ground squirrels by testosterone production required for spermatogenesis and activated by the circannual clock. Assessing surface conditions to decide when to terminate hibernation may help buffer these threatened squirrels against climate change. Documenting the extent to which other hibernators can facultatively alter emergence timing by reentering torpor after emergence will help identify which species are most likely to persist under climate change.
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27
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Song Z, Griesser M, Schuppli C, van Schaik CP. Does the expensive brain hypothesis apply to amphibians and reptiles? BMC Ecol Evol 2023; 23:77. [PMID: 38114918 PMCID: PMC10729550 DOI: 10.1186/s12862-023-02188-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 12/09/2023] [Indexed: 12/21/2023] Open
Abstract
Vertebrate brains show extensive variation in relative size. The expensive brain hypothesis argues that one important source of this variation is linked to a species' ability to generate the energy required to sustain the brain, especially during periods of unavoidable food scarcity. Here we ask whether this hypothesis, tested so far in endothermic vertebrates, also applies to ectotherms, where ambient temperature is an additional major aspect of energy balance. Phylogenetic comparative analyses of reptiles and amphibians support the hypothesis. First, relative brain size increases with higher body temperature in those species active during the day that can gain free energy by basking. Second, relative brain size is smaller among nocturnal species, which generally face less favorable energy budgets, especially when maintaining high body temperature. However, we do not find an effect of seasonal variation in ambient temperature or food on brain size, unlike in endotherms. We conclude that the factors affecting energy balance in ectotherms and endotherms are overlapping but not identical. We therefore discuss the idea that when body temperatures are seasonally very low, cognitive benefits may be thwarted and selection on larger brain size may be rare. Indeed, mammalian hibernators may show similarities to ectotherms.
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Affiliation(s)
- Zitan Song
- Comparative Socioecology group, Department for the Ecology of Animal Societies, Max Planck Institute for Animal Behavior, 78467, Konstanz, Germany.
| | - Michael Griesser
- Department of Biology, University of Konstanz, 78467, Konstanz, Germany
- Centre for the Advanced Study of Collective Behaviour, University of Konstanz, 78467, Konstanz, Germany
- Department of Collective Behavior, Max Planck Institute of Animal Behavior, 78467, Konstanz, Germany
| | - Caroline Schuppli
- Development and Evolution of Cognition Group, Max Planck Institute for Animal Behavior, 78467, Konstanz, Germany
| | - Carel P van Schaik
- Comparative Socioecology group, Department for the Ecology of Animal Societies, Max Planck Institute for Animal Behavior, 78467, Konstanz, Germany
- Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, 8057, Switzerland
- Center for the Interdisciplinary Study of language Evolution, University of Zurich, Zurich, 8057, Switzerland
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28
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Li A, Leng H, Li Z, Jin L, Sun K, Feng J. Temporal dynamics of the bat wing transcriptome: Insight into gene-expression changes that enable protection against pathogen. Virulence 2023; 14:2156185. [PMID: 36599840 PMCID: PMC9815227 DOI: 10.1080/21505594.2022.2156185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Skin acts as a mechanical barrier between the body and its surrounding environment and plays an important role in resistance to pathogens. However, we still know little regarding skin responses to physiological changes, particularly with regard to responses against potential pathogens. We herein executed RNA-seq on the wing of the Rhinolophus ferrumequinum to assess gene-expression variations at four physiological stages: pre-hibernation, hibernation (early-hibernation and late-hibernation), and post-hibernation, as well as the gene-expression patterns of infected and uninfected bats with the Pseudogymnoascus destructans (Pd). Our results showed that a greater number of differentially expressed genes between the more disparate physiological stages. Functional enrichment analysis showed that the down-regulated response pathways in hibernating bats included phosphorus metabolism and immune response, indicating metabolic suppression and decreased whole immune function. We also found up-regulated genes in post-hibernating bats that included C-type lectin receptor signalling, Toll-like receptor signalling pathway, and cell adhesion, suggesting that the immune response and skin integrity of the wing were improved after bats emerged from their hibernation and that this facilitated clearing Pd from the integument. Additionally, we found that the genes involved in cytokine or chemokine activity were up-regulated in late-hibernation compared to early-hibernation and that FOSB regulation of immune cell activation was differentially expressed in bats infected with Pd during late-hibernation, implying that the host's innate immune function was enhanced during late-hibernation so as to resist pathogenic infection. Our findings highlight the concept that maintenance of intrinsic immunity provides protection against pathogenic infections in highly resistant bats.
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Affiliation(s)
- Aoqiang Li
- Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China,School of Life Sciences, Central China Normal University, Wuhan, China
| | - Haixia Leng
- Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China
| | - Zhongle Li
- Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China,College of Life Science, Jilin Agricultural University, Changchun, China
| | - Longru Jin
- Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China
| | - Keping Sun
- Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China,CONTACT Keping Sun
| | - Jiang Feng
- Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China,College of Life Science, Jilin Agricultural University, Changchun, China,Jiang Feng
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29
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Popov IV, Berezinskaia IS, Popov IV, Martiusheva IB, Tkacheva EV, Gorobets VE, Tikhmeneva IA, Aleshukina AV, Tverdokhlebova TI, Chikindas ML, Venema K, Ermakov AM. Cultivable Gut Microbiota in Synanthropic Bats: Shifts of Its Composition and Diversity Associated with Hibernation. Animals (Basel) 2023; 13:3658. [PMID: 38067008 PMCID: PMC10705225 DOI: 10.3390/ani13233658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/15/2023] [Accepted: 11/24/2023] [Indexed: 01/14/2024] Open
Abstract
The role of bats in the global microbial ecology no doubt is significant due to their unique immune responses, ability to fly, and long lifespan, all contributing to pathogen spread. Some of these animals hibernate during winter, which results in the altering of their physiology. However, gut microbiota shifts during hibernation is little studied. In this research, we studied cultivable gut microbiota composition and diversity of Nyctalus noctula before, during, and after hibernation in a bat rehabilitation center. Gut microorganisms were isolated on a broad spectrum of culture media, counted, and identified with mass spectrometry. Linear modeling was used to investigate associations between microorganism abundance and N. noctula physiological status, and alpha- and beta-diversity indexes were used to explore diversity changes. As a result, most notable changes were observed in Serratia liquefaciens, Hafnia alvei, Staphylococcus sciuri, and Staphylococcus xylosus, which were significantly more highly abundant in hibernating bats, while Citrobacter freundii, Klebsiella oxytoca, Providencia rettgeri, Citrobacter braakii, and Pedicoccus pentosaceus were more abundant in active bats before hibernation. The alpha-diversity was the lowest in hibernating bats, while the beta-diversity differed significantly among all studied periods. Overall, this study shows that hibernation contributes to changes in bat cultivable gut microbiota composition and diversity.
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Affiliation(s)
- Igor V. Popov
- Faculty “Bioengineering and Veterinary Medicine” and Center for Agrobiotechnology, Don State Technical University, 344000 Rostov-on-Don, Russia; (I.V.P.); (E.V.T.); (V.E.G.); (I.A.T.); (M.L.C.); (A.M.E.)
- Division of Immunobiology and Biomedicine, Center of Genetics and Life Sciences, Sirius University of Science and Technology, 354340 Federal Territory Sirius, Russia
- Centre for Healthy Eating & Food Innovation (HEFI), Maastricht University—Campus Venlo, 5928 SZ Venlo, The Netherlands;
| | - Iraida S. Berezinskaia
- Rostov Research Institute of Microbiology and Parasitology, 344010 Rostov-on-Don, Russia; (I.S.B.); (I.B.M.); (A.V.A.)
| | - Ilia V. Popov
- Faculty “Bioengineering and Veterinary Medicine” and Center for Agrobiotechnology, Don State Technical University, 344000 Rostov-on-Don, Russia; (I.V.P.); (E.V.T.); (V.E.G.); (I.A.T.); (M.L.C.); (A.M.E.)
| | - Irina B. Martiusheva
- Rostov Research Institute of Microbiology and Parasitology, 344010 Rostov-on-Don, Russia; (I.S.B.); (I.B.M.); (A.V.A.)
| | - Elizaveta V. Tkacheva
- Faculty “Bioengineering and Veterinary Medicine” and Center for Agrobiotechnology, Don State Technical University, 344000 Rostov-on-Don, Russia; (I.V.P.); (E.V.T.); (V.E.G.); (I.A.T.); (M.L.C.); (A.M.E.)
| | - Vladislav E. Gorobets
- Faculty “Bioengineering and Veterinary Medicine” and Center for Agrobiotechnology, Don State Technical University, 344000 Rostov-on-Don, Russia; (I.V.P.); (E.V.T.); (V.E.G.); (I.A.T.); (M.L.C.); (A.M.E.)
| | - Iuliia A. Tikhmeneva
- Faculty “Bioengineering and Veterinary Medicine” and Center for Agrobiotechnology, Don State Technical University, 344000 Rostov-on-Don, Russia; (I.V.P.); (E.V.T.); (V.E.G.); (I.A.T.); (M.L.C.); (A.M.E.)
| | - Anna V. Aleshukina
- Rostov Research Institute of Microbiology and Parasitology, 344010 Rostov-on-Don, Russia; (I.S.B.); (I.B.M.); (A.V.A.)
| | - Tatiana I. Tverdokhlebova
- Rostov Research Institute of Microbiology and Parasitology, 344010 Rostov-on-Don, Russia; (I.S.B.); (I.B.M.); (A.V.A.)
| | - Michael L. Chikindas
- Faculty “Bioengineering and Veterinary Medicine” and Center for Agrobiotechnology, Don State Technical University, 344000 Rostov-on-Don, Russia; (I.V.P.); (E.V.T.); (V.E.G.); (I.A.T.); (M.L.C.); (A.M.E.)
- Health Promoting Naturals Laboratory, School of Environmental and Biological Sciences, Rutgers State University, New Brunswick, NJ 08901, USA
- Department of General Hygiene, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Koen Venema
- Centre for Healthy Eating & Food Innovation (HEFI), Maastricht University—Campus Venlo, 5928 SZ Venlo, The Netherlands;
| | - Alexey M. Ermakov
- Faculty “Bioengineering and Veterinary Medicine” and Center for Agrobiotechnology, Don State Technical University, 344000 Rostov-on-Don, Russia; (I.V.P.); (E.V.T.); (V.E.G.); (I.A.T.); (M.L.C.); (A.M.E.)
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30
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Wang H, Guo Y, Yan W, Cao L, Bai X, Zhao J, Dang K, Gao Y. Weakened Contractile Performance and Mitochondrial Respiratory Complex Activity in Skeletal Muscle Improve during Interbout Arousal in Hibernating Daurian Ground Squirrel, Spermophilus dauricus. Int J Mol Sci 2023; 24:15785. [PMID: 37958769 PMCID: PMC10650195 DOI: 10.3390/ijms242115785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 10/28/2023] [Accepted: 10/29/2023] [Indexed: 11/15/2023] Open
Abstract
Mammalian hibernation is composed of multiple episodes of torpor bout, separated by phases of interbout arousal. During torpor, the skeletal muscles of mammals are undoubtedly inactive, but it has been proven to mitigate disuse atrophy. While interbout arousal has been implicated in the prevention of muscle atrophy, the underlying mechanisms sustaining muscle contraction remain to be explored. In the present study, Daurian ground squirrels (Spermophilus dauricus) were divided into four groups: pre-hibernation (PRE), torpor (TOR), interbout arousal (IBA), and post-hibernation (POST). The contractile performance of slow-twitch soleus muscle (SOL) and fast-twitch extensor digitorum longus muscle (EDL) was detected both in situ and in vitro. Concurrently, mitochondrial respiratory chain complex activity in these muscles was quantified. Our findings revealed that in situ contractile properties of both muscles, including force, power output, time duration, and force development/relaxation rates of twitch contraction, and force and power output of tetanic contraction declined in the TOR group compared to the PRE group, but improved in the IBA and POST groups. Fatigue resistance of muscles, determined by the power output of repetitive tetanic contractions in situ, decreased in the TOR group but recovered in the IBA and POST groups. In vitro studies demonstrated that tetanic contraction power output in isolated muscles increased with muscle temperature in both TOR and IBA groups. However, at the same temperature, power output was consistently lower in the TOR group compared to the IBA group. Moreover, the activity of the mitochondrial respiratory chain complex, especially Complexes I and II, decreased in the TOR group but showed recovery in the IBA and POST groups. These findings suggest that both the contractile performance and fatigue resistance of mammalian skeletal muscle are compromised during torpor but can be improved during interbout arousal and post-hibernation. The rebound in body temperature and rise in mitochondrial respiratory chain complex activity in skeletal muscle are involved in enhancing contractile performance and fatigue resistance. This study suggests that interbout arousal functions as a vital temporal interval during which skeletal muscles can transition from the inactivity induced by torpor to a state of restored contractile functionality. Thus, interbout arousal serves as a behavioral safeguard against disuse-induced damage to skeletal muscles during hibernation.
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Affiliation(s)
- Huiping Wang
- Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi’an 710069, China; (H.W.); (Y.G.); (W.Y.); (L.C.); (X.B.); (J.Z.)
- Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an 710069, China
| | - Yuxi Guo
- Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi’an 710069, China; (H.W.); (Y.G.); (W.Y.); (L.C.); (X.B.); (J.Z.)
- Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an 710069, China
| | - Wenjing Yan
- Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi’an 710069, China; (H.W.); (Y.G.); (W.Y.); (L.C.); (X.B.); (J.Z.)
- Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an 710069, China
| | - Liqi Cao
- Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi’an 710069, China; (H.W.); (Y.G.); (W.Y.); (L.C.); (X.B.); (J.Z.)
- Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an 710069, China
| | - Xiaozhuo Bai
- Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi’an 710069, China; (H.W.); (Y.G.); (W.Y.); (L.C.); (X.B.); (J.Z.)
- Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an 710069, China
| | - Jing Zhao
- Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi’an 710069, China; (H.W.); (Y.G.); (W.Y.); (L.C.); (X.B.); (J.Z.)
- Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an 710069, China
| | - Kai Dang
- Lab for Bone Metabolism, Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
| | - Yunfang Gao
- Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi’an 710069, China; (H.W.); (Y.G.); (W.Y.); (L.C.); (X.B.); (J.Z.)
- Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an 710069, China
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Smith LL. Similarities and differences regarding acute anorexia nervosa and semi-starvation: does behavioral thermoregulation play a central role? Front Behav Neurosci 2023; 17:1243572. [PMID: 37953827 PMCID: PMC10634530 DOI: 10.3389/fnbeh.2023.1243572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 09/22/2023] [Indexed: 11/14/2023] Open
Abstract
Objective To clarify the association between acute anorexia nervosa (AN) and semi-starvation (SS) by focusing on similarities and differences in physiology, mood, and behavior. Method A comparison of published literature between these two groups. Results Both groups show similar hormonal and metabolic changes in response to caloric restriction and extreme weight loss (~25%). Associated changes result in a reduced body temperature (Tcore-low). Maintenance of body temperature within a specific range is crucial to survival. However, both groups cannot activate autonomic strategies to maintain their Tcore-low, such as increasing metabolic rate, constricting skin blood vessels, or shivering. Furthermore, Tcore-low increases the individuals' "coldness sensations" throughout the body, hence the frequent reports from ANs and SSs of "feeling cold." To eliminate these uncomfortable "coldness sensations" and, importantly, to maintain Tcore-low, ANs, and SSs "select" different thermoregulatory behavioral strategies. It is proposed that the primary differences between AN and SS, based on genetics, now manifest due to the "selection" of different thermo-regulatory behaviors. AN patients (ANs) "select" hyperactive behavior (HyAc), which increases internal metabolic heat and thus assists with maintaining Tcore-low; in harmony with hyperactive behavior is a lively mood. Also related to this elevated arousal pattern, ANs experience disrupted sleep. In contrast, SS individuals "select" a passive thermo-behavioral strategy, "shallow torpor," which includes reduced activity, resulting in energy conservation. In addition, this inactivity aids in the retention of generated metabolic heat. Corresponding to this lethargic behavior, SS individuals display a listless mood and increased sleep. Conclusion Initial similarities between the two are attributable to physiological changes related to extreme weight loss. Differences are most likely attributable to genetically programmed "selection" of alternate thermoregulatory strategies, primarily to maintain Tcore-low. However, if acute AN is prolonged and evolves into a chronic condition, AN will more closely align with starvation and more precisely reflect SS symptomology.
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Affiliation(s)
- Lucille Lakier Smith
- Human Performance Laboratory, Department of Kinesiology, School of Health Sciences, East Carolina University, Greenville, NC, United States
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32
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Power ML, Ransome RD, Riquier S, Romaine L, Jones G, Teeling EC. Hibernation telomere dynamics in a shifting climate: insights from wild greater horseshoe bats. Proc Biol Sci 2023; 290:20231589. [PMID: 37817598 PMCID: PMC10565397 DOI: 10.1098/rspb.2023.1589] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 09/10/2023] [Indexed: 10/12/2023] Open
Abstract
Hibernation is linked with various hypotheses to explain the extended lifespan of hibernating mammals compared with their non-hibernating counterparts. Studies on telomeres, markers of ageing and somatic maintenance, suggest telomere shortening slows during hibernation, and lengthening may reflect self-maintenance with favourable conditions. Bats in temperate zones adjust body temperatures during winter torpor to conserve energy and exploit mild conditions for foraging. Climate change may impact the hibernation cycle of bats, but more research is needed regarding the role of telomeres in understanding their response to a changing climate. Here, relative telomere length (rTL) was measured in the long-lived greater horseshoe bat Rhinolophus ferrumequinum (n = 223 individuals) over three winters, considering climatic conditions. Cross-sectional analyses revealed between-individual variation in rTL with a strong year effect, likely linked to varying weather conditions and foraging success. Additionally, within-individual increases of rTL occurred in 51% of consecutive measurements, with evidence of increasing telomerase expression during hibernation in this species. These findings highlight the beneficial effects of hibernation on telomeres and potential consequences of changing climatic conditions for long-lived temperate bats. Understanding the interplay between hibernation, telomeres, and climate can provide insights into the adaptive capacity and survival of bat populations facing environmental challenges.
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Affiliation(s)
- Megan L Power
- School of Biology and Environmental Science, Science Centre West, University College Dublin, Belfield, Dublin 4, Republic of Ireland
| | - Roger D Ransome
- School of Biological Sciences, University of Bristol, Life Sciences Building, 24 Tyndall Avenue, Bristol BS8 1TQ, UK
| | - Sébastien Riquier
- School of Biology and Environmental Science, Science Centre West, University College Dublin, Belfield, Dublin 4, Republic of Ireland
| | - Luke Romaine
- School of Biological Sciences, University of Bristol, Life Sciences Building, 24 Tyndall Avenue, Bristol BS8 1TQ, UK
| | - Gareth Jones
- School of Biological Sciences, University of Bristol, Life Sciences Building, 24 Tyndall Avenue, Bristol BS8 1TQ, UK
| | - Emma C Teeling
- School of Biology and Environmental Science, Science Centre West, University College Dublin, Belfield, Dublin 4, Republic of Ireland
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Blanco MB, Greene LK, Ellsaesser LN, Williams CV, Ostrowski CA, Davison MM, Welser K, Klopfer PH. Seasonal variation in glucose and insulin is modulated by food and temperature conditions in a hibernating primate. Front Physiol 2023; 14:1251042. [PMID: 37745231 PMCID: PMC10512831 DOI: 10.3389/fphys.2023.1251042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 08/23/2023] [Indexed: 09/26/2023] Open
Abstract
Feast-fast cycles allow animals to live in seasonal environments by promoting fat storage when food is plentiful and lipolysis when food is scarce. Fat-storing hibernators have mastered this cycle over a circannual schedule, by undergoing extreme fattening to stockpile fuel for the ensuing hibernation season. Insulin is intrinsic to carbohydrate and lipid metabolism and is central to regulating feast-fast cycles in mammalian hibernators. Here, we examine glucose and insulin dynamics across the feast-fast cycle in fat-tailed dwarf lemurs, the only obligate hibernator among primates. Unlike cold-adapted hibernators, dwarf lemurs inhabit tropical forests in Madagascar and hibernate under various temperature conditions. Using the captive colony at the Duke Lemur Center, we determined fasting glucose and insulin, and glucose tolerance, in dwarf lemurs across seasons. During the lean season, we maintained dwarf lemurs under stable warm, stable cold, or fluctuating ambient temperatures that variably included food provisioning or deprivation. Overall, we find that dwarf lemurs can show signatures of reversible, lean-season insulin resistance. During the fattening season prior to hibernation, dwarf lemurs had low glucose, insulin, and HOMA-IR despite consuming high-sugar diets. In the active season after hibernation, glucose, insulin, HOMA-IR, and glucose tolerance all increased, highlighting the metabolic processes at play during periods of weight gain versus weight loss. During the lean season, glucose remained low, but insulin and HOMA-IR increased, particularly in animals kept under warm conditions with daily food. Moreover, these lemurs had the greatest glucose intolerance in our study and had average HOMA-IR values consistent with insulin resistance (5.49), while those without food under cold (1.95) or fluctuating (1.17) temperatures did not. Remarkably low insulin in dwarf lemurs under fluctuating temperatures raises new questions about lipid metabolism when animals can passively warm and cool rather than undergo sporadic arousals. Our results underscore that seasonal changes in insulin and glucose tolerance are likely hallmarks of hibernating mammals. Because dwarf lemurs can hibernate under a range of conditions in captivity, they are an emerging model for primate metabolic flexibility with implications for human health.
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Affiliation(s)
- Marina B. Blanco
- Duke Lemur Center, Durham, NC, United States
- Department of Biology, Duke University, Durham, NC, United States
| | - Lydia K. Greene
- Duke Lemur Center, Durham, NC, United States
- Department of Biology, Duke University, Durham, NC, United States
| | | | | | | | | | - Kay Welser
- Duke Lemur Center, Durham, NC, United States
| | - Peter H. Klopfer
- Department of Biology, Duke University, Durham, NC, United States
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Sato T, Sugiyama T, Sekijima T. Mating in the cold. Prolonged sperm storage provides opportunities for forced copulation by male bats during winter. Front Physiol 2023; 14:1241470. [PMID: 37745243 PMCID: PMC10511888 DOI: 10.3389/fphys.2023.1241470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 08/28/2023] [Indexed: 09/26/2023] Open
Abstract
In a wide range of heterothermic mammals, hibernation interrupts the reproductive cycle by forcing reproductive delays. In hibernating bats with delayed fertilization, an opportunity for sperm competition is enhanced by extending a time-window between copulations and fertilization. In order to achieve greater fertilization success, males are expected to show adaptations for sperm competition by increasing their opportunities for mating over an extended period. We aimed to clarify the physiological and behavioral characteristics of male bats experiencing increased risks of sperm competition. We investigated the characteristics of the reproductive cycle of the little horseshoe bat (Rhinolophus cornutus), and examined whether males retain reproductive physiology related to sexual behavior, and attempt to copulate with females even during the hibernation period. Field observations and histological examinations of the reproductive cycle confirmed that females, having mated in the autumn, store spermatozoa in the uterus during hibernation and give birth in the early summer to just one offspring per year, thus males face a low certainty of successful fertilization. Although their testes regressed rapidly and their testosterone levels were lower during winter than in autumn, males stored motile spermatozoa in their cauda epididymides from autumn throughout the winter. During hibernation, we found that males occasionally aroused from torpor and attempted to mate forcibly with torpid females. Forced copulations appear to increase a male's chances of obtaining a mate while avoiding pre-copulatory female choice. Epididymal sperm storage could be advantageous for males in allowing them to extend their potential mating period even though their testes have regressed. We also found that some hibernating nulliparous females were ready for fertilization in spring after hibernation, whereas few parous females appeared in the same roost. In contrast to males, forced copulations would be maladaptive for females because they cannot opt for higher-quality males while in torpor. Females that have experienced sexual coercion when young may subsequently avoid hibernacula where adult males are present.
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Affiliation(s)
- Takahiro Sato
- Graduate School of Technology, Industrial, and Social Sciences, Tokushima University, Tokushima, Japan
- Faculty of Agriculture, Niigata University, Niigata, Japan
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Kamata T, Yamada S, Sekijima T. Differential AMPK-mediated metabolic regulation observed in hibernation-style polymorphisms in Siberian chipmunks. Front Physiol 2023; 14:1220058. [PMID: 37664438 PMCID: PMC10468594 DOI: 10.3389/fphys.2023.1220058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 08/07/2023] [Indexed: 09/05/2023] Open
Abstract
Hibernation is a unique physiological phenomenon allowing extreme hypothermia in endothermic mammals. Hypometabolism and hypothermia tolerance in hibernating animals have been investigated with particular interest; recently, studies of cultured cells and manipulation of the nervous system have made it possible to reproduce physiological states related to hypothermia induction. However, much remains unknown about the periodic regulation of hibernation. In particular, the physiological mechanisms facilitating the switch from an active state to a hibernation period, including behavioral changes and the acquisition of hypothermia tolerance remain to be elucidated. AMPK is a protein known to play a central role not only in feeding behavior but also in metabolic regulation in response to starvation. Our previous research has revealed that chipmunks activate AMPK in the brain during hibernation. However, whether AMPK is activated during winter in non-hibernating animals is unknown. Previous comparative studies between hibernating and non-hibernating animals have often been conducted between different species, consequently it has been impossible to account for the effects of phylogenetic differences. Our long-term monitoring of siberian chipmunks, has revealed intraspecific variation between those individuals that hibernate annually and those that never become hypothermic. Apparent differences were found between hibernating and non-hibernating types with seasonal changes in lifespan and blood HP levels. By comparing seasonal changes in AMPK activity between these polymorphisms, we clarified the relationship between hibernation and AMPK regulation. In hibernating types, phosphorylation of p-AMPK and p-ACC was enhanced throughout the brain during hibernation, indicating that AMPK-mediated metabolic regulation is activated. In non-hibernating types, AMPK and ACC were not seasonally activated. In addition, AMPK activation in the hypothalamus had already begun during high Tb before hibernation. Changes in AMPK activity in the brain during hibernation may be driven by circannual rhythms, suggesting a hibernation-regulatory mechanism involving AMPK activation independent of Tb. The differences in brain AMPK regulation between hibernators and non-hibernators revealed in this study were based on a single species thus did not involve phylogenetic differences, thereby supporting the importance of brain temperature-independent AMPK activation in regulating seasonal metabolism in hibernating animals.
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Affiliation(s)
- Taito Kamata
- Graduate School of Science and Technology, Niigata University, Niigata, Japan
- Faculty of Agriculture, Niigata University, Niigata, Japan
| | - Shintaro Yamada
- Graduate School of Science and Technology, Niigata University, Niigata, Japan
- Institute of Biomedical Science, Kansai Medical University, Osaka, Japan
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Hong X, Wang Y, Wang K, Wei C, Li W, Yu L, Xu H, Zhu J, Zhu X, Liu X. Single-Cell Atlas Reveals the Hemocyte Subpopulations and Stress Responses in Asian Giant Softshell Turtle during Hibernation. BIOLOGY 2023; 12:994. [PMID: 37508424 PMCID: PMC10376416 DOI: 10.3390/biology12070994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/16/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023]
Abstract
Hibernation in turtle species is an adaptive survival strategy to colder winter conditions or food restrictions. However, the mechanisms underlying seasonal adaptions remain unclear. In the present study, we collected hemocytes from Pelochelys cantorii and compared the molecular signature of these cells between the active state and hibernation period based on single-cell RNA sequencing (scRNA-seq) analysis. We found six cell types and identified a list of new marker genes for each cell subpopulation. Moreover, several heat shock genes, including the Hsp40 family chaperone gene (DNAJ) and HSP temperature-responsive genes (HSPs), were upregulated during the hibernation period, which predicted these genes may play crucial roles in the stress response during hibernation. Additionally, compared to hemocytes in the active state, several upregulated differentially expressed immune-related genes, such as stat1, traf3, and socs6, were identified in hemocytes during the hibernation period, thus indicating the important immune function of hemocytes. Therefore, our findings provide a unified classification of P. cantorii hemocytes and identify the genes related to the stress response, thereby providing a better understanding of the adaptive mechanisms of hibernation.
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Affiliation(s)
- Xiaoyou Hong
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
| | - Yakun Wang
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
| | - Kaikuo Wang
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
- College of Life Science and Fisheries, Shanghai Ocean University, Shanghai 201306, China
| | - Chengqing Wei
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
| | - Wei Li
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
| | - Lingyun Yu
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
| | - Haoyang Xu
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
- College of Life Science and Fisheries, Shanghai Ocean University, Shanghai 201306, China
| | - Junxian Zhu
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
- College of Life Science and Fisheries, Shanghai Ocean University, Shanghai 201306, China
| | - Xinping Zhu
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
- College of Life Science and Fisheries, Shanghai Ocean University, Shanghai 201306, China
| | - Xiaoli Liu
- Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
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37
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Fu K, Hui C, Wang X, Ji T, Li X, Sun R, Xing C, Fan X, Gao Y, Su L. Torpor-like Hypothermia Induced by A1 Adenosine Receptor Agonist: A Novel Approach to Protect against Neuroinflammation. Int J Mol Sci 2023; 24:11036. [PMID: 37446216 DOI: 10.3390/ijms241311036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 06/27/2023] [Accepted: 06/29/2023] [Indexed: 07/15/2023] Open
Abstract
Hypothermia is a promising clinical therapy for acute injuries, including neural damage, but it also faces practical limitations due to the complexities of the equipment and procedures required. This study investigates the use of the A1 adenosine receptor (A1AR) agonist N6-cyclohexyladenosine (CHA) as a more accessible method to induce steady, torpor-like hypothermic states. Additionally, this study investigates the protective potential of CHA against LPS-induced sepsis and neuroinflammation. Our results reveal that CHA can successfully induce a hypothermic state by activating a neuronal circuit similar to the one that induces physiological torpor. This state is characterized by maintaining a steady core body temperature below 28 °C. We further found that this torpor-like state effectively mitigates neuroinflammation and preserves the integrity of the blood-brain barrier during sepsis, thereby limiting the infiltration of inflammatory factors into the central nervous system. Instead of being a direct effect of CHA, this protective effect is attributed to inhibiting pro-inflammatory responses in macrophages and reducing oxidative stress damage in endothelial cells under systemic hypothermia. These results suggest that A1AR agonists such as CHA could potentially be potent neuroprotective agents against neuroinflammation. They also shed light on possible future directions for the application of hypothermia-based therapies in the treatment of sepsis and other neuroinflammatory conditions.
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Affiliation(s)
- Kang Fu
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Chunlei Hui
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
| | - Xinyuan Wang
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Tingting Ji
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Xiuqing Li
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Rui Sun
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Chunlei Xing
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
| | - Xi Fan
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yuanqing Gao
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Li Su
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
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38
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Perry BW, Saxton MW, Jansen HT, Quackenbush CR, Evans Hutzenbiler BD, Robbins CT, Kelley JL, Cornejo OE. A multi-tissue gene expression dataset for hibernating brown bears. BMC Genom Data 2023; 24:33. [PMID: 37291509 PMCID: PMC10251632 DOI: 10.1186/s12863-023-01136-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 06/06/2023] [Indexed: 06/10/2023] Open
Abstract
OBJECTIVES Complex physiological adaptations often involve the coordination of molecular responses across multiple tissues. Establishing transcriptomic resources for non-traditional model organisms with phenotypes of interest can provide a foundation for understanding the genomic basis of these phenotypes, and the degree to which these resemble, or contrast, those of traditional model organisms. Here, we present a one-of-a-kind gene expression dataset generated from multiple tissues of two hibernating brown bears (Ursus arctos). DATA DESCRIPTION This dataset is comprised of 26 samples collected from 13 tissues of two hibernating brown bears. These samples were collected opportunistically and are typically not possible to attain, resulting in a highly unique and valuable gene expression dataset. In combination with previously published datasets, this new transcriptomic resource will facilitate detailed investigation of hibernation physiology in bears, and the potential to translate aspects of this biology to treat human disease.
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Affiliation(s)
- Blair W Perry
- School of Biological Sciences, Washington State University, Pullman, WA, 99164, USA
| | - Michael W Saxton
- School of Biological Sciences, Washington State University, Pullman, WA, 99164, USA
| | - Heiko T Jansen
- Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, 99164, USA
| | - Corey R Quackenbush
- School of Biological Sciences, Washington State University, Pullman, WA, 99164, USA
| | | | - Charles T Robbins
- School of Biological Sciences, Washington State University, Pullman, WA, 99164, USA
- School of the Environment, Washington State University, Pullman, WA, 99164, USA
| | - Joanna L Kelley
- Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, CA, 95060, USA
| | - Omar E Cornejo
- Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, CA, 95060, USA.
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Lin R, Wu J, You Z, Xu D, Li C, Wang W, Qian G. Induction of Hibernation and Changes in Physiological and Metabolic Indices in Pelodiscus sinensis. BIOLOGY 2023; 12:biology12050720. [PMID: 37237532 DOI: 10.3390/biology12050720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/02/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023]
Abstract
Pelodiscus sinensis (P. sinensis) is a commonly cultivated turtle species with a habit of hibernation. To study the changes in histone expression and methylation of P. sinensis during hibernation induction, a model was established by artificial induction. Physiological and metabolic indices were measured, and the expression and localization of histone (H1, H2A, H2B, H3, and H4) and methylation-related genes (ASH2L, KMT2A, KMT2E, KDM1A, KDM1B, and KDM5A) were measured by quantitative PCR, immunohistochemistry, and Western blot analysis. The results indicated that the metabolism, antioxidation index, and relative expression of histone methyltransferase were significantly decreased (p < 0.05), whereas the activity and expression of histone demethyltransferase were significantly increased (p < 0.05). Although our results showed significant changes in physiological and gene expression after hibernation induction, we could not confirm that P. sinensis entered deep hibernation. Therefore, for the state after cooling-induced hibernation, cold torpor might be a more accurate description. The results indicate that the P. sinensis can enter cold torpor through artificial induction, and the expression of histones may promote gene transcription. Unlike histones expressed under normal conditions, histone methylation may activate gene transcription during hibernation induction. Western blot analysis revealed that the ASH2L and KDM5A proteins were differentially expressed in the testis at different months (p < 0.05), which may perform a role in regulating gene transcription. The immunohistochemical localization of ASH2L and KDM5A in spermatogonia and spermatozoa suggests that ASH2L and KDM5A may perform a role in mitosis and meiosis. In conclusion, this study is the first to report changes in histone-related genes in reptiles, which provides insight for further studies on the physiological metabolism and histone methylation regulation of P. sinensis during the hibernation induction and hibernation period.
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Affiliation(s)
- Runlan Lin
- College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China
- College of Biology and Environment, Zhejiang Wanli University, Ningbo 315100, China
| | - Jiahao Wu
- College of Biology and Environment, Zhejiang Wanli University, Ningbo 315100, China
| | - Ziyi You
- College of Biology and Environment, Zhejiang Wanli University, Ningbo 315100, China
| | - Dongjie Xu
- College of Biology and Environment, Zhejiang Wanli University, Ningbo 315100, China
| | - Caiyan Li
- College of Biology and Environment, Zhejiang Wanli University, Ningbo 315100, China
| | - Wei Wang
- College of Biology and Environment, Zhejiang Wanli University, Ningbo 315100, China
| | - Guoying Qian
- College of Biology and Environment, Zhejiang Wanli University, Ningbo 315100, China
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40
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Koch M, Manecke J, Burgard JP, Münnich R, Kugelschafter K, Kiefer A, Veith M. How weather triggers the emergence of bats from their subterranean hibernacula. Sci Rep 2023; 13:6344. [PMID: 37072427 PMCID: PMC10113228 DOI: 10.1038/s41598-023-32166-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 03/23/2023] [Indexed: 05/03/2023] Open
Abstract
Hibernation is one of the most important behaviours of bats of the temperate zone. During winter, when little food or liquid water is available, hibernation in torpor lowers metabolic costs. However, the timing of emergence from hibernation is crucial for the resumption of the reproductive process in spring. Here, we investigate the spring emergence of six bat species or pairs of bat species of the genera Myotis and Plecotus at five hibernation sites in Central Europe over 5 years. Using generalized additive Poisson models (GAPMs), we analyze the influence of weather conditions (air and soil temperature, atmospheric pressure, atmospheric pressure trend, rain, wind, and cloud cover) as predictors of bat activity and separate these extrinsic triggers from residual motivation to emerge from hibernation (extrinsic factors not studied; intrinsic motivation). Although bats in a subterranean hibernaculum are more or less cut off from the outside world, all species showed weather dependence, albeit to varying degrees, with air temperature outside the hibernaculum having a significant positive effect in all species. The residual, potentially intrinsic motivation of species to emerge from their hibernacula corresponds to their general ecological adaptation, such as trophic specialization and roosting preferences. It allows the definition of three functional groups (high, medium and low residual activity groups) according to the degree of weather dependence of spring activity. A better knowledge of the interplay of extrinsic triggers and residual motivation (e.g., internal zeitgebers) for spring emergence will help to understand the flexibility of a species to adapt to a changing world.
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Affiliation(s)
- Martin Koch
- Department of Biogeography, Trier University, Universitätsring 15, 54296 Trier, Germany
| | - Julia Manecke
- Economics and Social Statistics Department, Trier University, Universitätsring 15, 54296 Trier, Germany
| | - Jan Pablo Burgard
- Economics and Social Statistics Department, Trier University, Universitätsring 15, 54296 Trier, Germany
| | - Ralf Münnich
- Economics and Social Statistics Department, Trier University, Universitätsring 15, 54296 Trier, Germany
| | | | - Andreas Kiefer
- Department of Biogeography, Trier University, Universitätsring 15, 54296 Trier, Germany
- NABU Rhineland-Palatinate, 55118 Mainz, Germany
| | - Michael Veith
- Department of Biogeography, Trier University, Universitätsring 15, 54296 Trier, Germany
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Tupone D, Hernan S, Chiavetta P, Morrison S, Cano G. Central circuit controlling thermoregulatory inversion and torpor-like state. RESEARCH SQUARE 2023:rs.3.rs-2698203. [PMID: 36993654 PMCID: PMC10055657 DOI: 10.21203/rs.3.rs-2698203/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
Abstract
To maintain core body temperature in mammals, the CNS thermoregulatory networks respond to cold exposure by increasing brown adipose tissue and shivering thermogenesis. However, in hibernation or torpor, this normal thermoregulatory response is supplanted by "thermoregulatory inversion", an altered homeostatic state in which cold exposure causes inhibition of thermogenesis and warm exposure stimulates thermogenesis. Here we demonstrate the existence of a novel, dynorphinergic thermoregulatory reflex pathway between the dorsolateral parabrachial nucleus and the dorsomedial hypothalamus that bypasses the normal thermoregulatory integrator in the hypothalamic preoptic area to play a critical role in mediating the inhibition of thermogenesis during thermoregulatory inversion. Our results indicate the existence of a neural circuit mechanism for thermoregulatory inversion within the CNS thermoregulatory pathways and support the potential for inducing a homeostatically-regulated, therapeutic hypothermia in non-hibernating species, including humans.
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Ma WX, Yuan PC, Zhang H, Kong LX, Lazarus M, Qu WM, Wang YQ, Huang ZL. Adenosine and P1 receptors: Key targets in the regulation of sleep, torpor, and hibernation. Front Pharmacol 2023; 14:1098976. [PMID: 36969831 PMCID: PMC10036772 DOI: 10.3389/fphar.2023.1098976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 02/27/2023] [Indexed: 03/12/2023] Open
Abstract
Graphical AbstractAdenosine mediates sleep, torpor and hibernation through P1 receptors. Recent reasearch has shown that P1 receptors play a vital role in the regulation of sleep-wake, torpor and hibernation-like states. In this review, we focus on the roles and neurobiological mechanisms of the CNS adenosine and P1 receptors in these three states. Among them, A1 and A2A receptors are key targets for sleep-wake regulation, A1Rs and A3Rs are very important for torpor induction, and activation of A1Rs is sufficient for hibernation-like state.
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Affiliation(s)
- Wei-Xiang Ma
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Department of Pharmacology, School of Basic Medical Sciences, Institutes of Brain Science, Fudan University, Shanghai, China
| | - Ping-Chuan Yuan
- Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, School of Pharmacy, Wannan Medical College, Wuhu, China
| | - Hui Zhang
- Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, School of Pharmacy, Wannan Medical College, Wuhu, China
| | - Ling-Xi Kong
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Department of Pharmacology, School of Basic Medical Sciences, Institutes of Brain Science, Fudan University, Shanghai, China
| | - Michael Lazarus
- International Institute for Integrative Sleep Medicine (WPI-IIIS) and Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Wei-Min Qu
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Department of Pharmacology, School of Basic Medical Sciences, Institutes of Brain Science, Fudan University, Shanghai, China
- *Correspondence: Wei-Min Qu, ; Yi-Qun Wang, ; Zhi-Li Huang,
| | - Yi-Qun Wang
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Department of Pharmacology, School of Basic Medical Sciences, Institutes of Brain Science, Fudan University, Shanghai, China
- *Correspondence: Wei-Min Qu, ; Yi-Qun Wang, ; Zhi-Li Huang,
| | - Zhi-Li Huang
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Department of Pharmacology, School of Basic Medical Sciences, Institutes of Brain Science, Fudan University, Shanghai, China
- *Correspondence: Wei-Min Qu, ; Yi-Qun Wang, ; Zhi-Li Huang,
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Stapelfeldt B, Tress C, Koch R, Tress J, Kerth G, Scheuerlein A. Long-term field study reveals that warmer summers lead to larger and longer-lived females only in northern populations of Natterer's bats. Oecologia 2023; 201:853-861. [PMID: 36773071 PMCID: PMC10038953 DOI: 10.1007/s00442-023-05318-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 01/07/2023] [Indexed: 02/12/2023]
Abstract
Animals often respond to climate change with changes in morphology, e.g., shrinking body size with increasing temperatures, as expected by Bergmann's rule. Because small body size can have fitness costs for individuals, this trend could threaten populations. Recent studies, however, show that morphological responses to climate change and the resulting fitness consequences cannot be generalized even among related species. In this long-term study, we investigate the interaction between ambient temperature, body size and survival probability in a large number of individually marked wild adult female Natterer's bats (Myotis nattereri). We compare populations from two geographical regions in Germany with a different climate. In a sliding window analysis, we found larger body sizes in adult females that were raised in warmer summers only in the northern population, but not in the southern population that experienced an overall warmer climate. With a capture-mark-recapture approach, we showed that larger individuals had higher survival rates, demonstrating that weather conditions in early life could have long-lasting fitness effects. The different responses in body size to warmer temperatures in the two regions highlight that fitness-relevant morphological responses to climate change have to be viewed on a regional scale and may affect local populations differently.
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Affiliation(s)
- Bianca Stapelfeldt
- Zoological Institute and Museum, University of Greifswald, Greifswald, Germany.
| | - Christoph Tress
- Fledermausforschungsprojekt Wooster Teerofen e.V., Wooster Teerofen, Germany
| | - Ralf Koch
- Naturpark Nossentiner/Schwinzer Heide, Plau am See OT Karow, Germany
| | - Johannes Tress
- Fledermausforschungsprojekt Wooster Teerofen e.V., Wooster Teerofen, Germany
| | - Gerald Kerth
- Zoological Institute and Museum, University of Greifswald, Greifswald, Germany
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Findlay‐Robinson R, Deecke VB, Weatherall A, Hill DL. Effects of climate change on life‐history traits in hibernating mammals. Mamm Rev 2023. [DOI: 10.1111/mam.12308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Rachel Findlay‐Robinson
- Institute of Science and the Environment, University of Cumbria, Ambleside Cumbria LA22 9BB UK
- School of Biodiversity, One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences University of Glasgow Glasgow G12 8QQ UK
| | - Volker B. Deecke
- Institute of Science and the Environment, University of Cumbria, Ambleside Cumbria LA22 9BB UK
| | - Andrew Weatherall
- Institute of Science and the Environment, University of Cumbria, Ambleside Cumbria LA22 9BB UK
| | - Davina L. Hill
- School of Biodiversity, One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences University of Glasgow Glasgow G12 8QQ UK
- School of Animal, Plant and Environmental Sciences University of the Witwatersrand Private Bag 3, Wits 2050 Johannesburg South Africa
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Song X, Zhai Y, Song J, Zhang J, Li X. The structural discrepancy between the small and large gut microbiota of Asiatic toad (Bufo gargarizans) during hibernation. Folia Microbiol (Praha) 2023:10.1007/s12223-023-01031-5. [PMID: 36637770 DOI: 10.1007/s12223-023-01031-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 01/01/2023] [Indexed: 01/14/2023]
Abstract
Hibernating amphibians are suitable for the research on the adaptation of gut microbiota to long-term fasting and cold stresses. However, the previous studies mainly focus on the large or whole gut microbiota but not the small gut microbiota. To test the structural discrepancy between the small and large gut microbiota during hibernation, we performed two independent batches of 16S rRNA gene amplicon sequencing to profile the small and large gut microbiota of hibernating Asiatic toad (Bufo gargarizans) from two wild populations. Both batches of data revealed that Proteobacteria, Bacteroidetes, and Firmicutes were the three most dominant phyla in the small and large gut microbiota. Three core OTUs with 100% occurrence in all gut microbiotas were annotated as Pseudomonas. A significant structural discrepancy was detected between the small and large gut microbiota. For instance, Proteobacteria assembled in the small intestine with a higher proportion than it did in the large intestine, but Bacteroidetes and Firmicutes assembled in the large intestine with a higher proportion than they did in the small intestine. The large gut microbiota exhibited higher diversity than the small gut microbiota. Nevertheless, a severe batch effect existed in the structural analysis of the gut microbiotas. The large gut microbiota showed a better resistance to the batch effect than the small gut microbiota did. This study provides preliminary evidence that microbes assemble in the small and large intestines of amphibians with discrepant patterns during hibernation.
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Affiliation(s)
- Xiaowei Song
- College of Software Engineering, Chengdu University of Information and Technology, Chengdu, Sichuan, China. .,College of Life Sciences, Institute for Conservation and Utilization of Agro-Bioresources in Dabie Mountains, Xinyang Normal University, Xinyang, Henan, China. .,CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan, China.
| | - Yuanyuan Zhai
- College of Life Sciences, Institute for Conservation and Utilization of Agro-Bioresources in Dabie Mountains, Xinyang Normal University, Xinyang, Henan, China
| | - Jinghan Song
- College of Life Sciences, Institute for Conservation and Utilization of Agro-Bioresources in Dabie Mountains, Xinyang Normal University, Xinyang, Henan, China
| | - Jingwei Zhang
- Hospital of Xinyang Normal University, Xinyang Normal University, Henan, Xinyang, China
| | - Xiangzhen Li
- CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan, China
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Reusch C, Scheuerlein A, Grosche L, Meier F, Gampe J, Dammhahn M, van Schaik J, Kerth G. The risk faced by the early bat: individual plasticity and mortality costs of the timing of spring departure after hibernation. OIKOS 2023. [DOI: 10.1111/oik.09654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Affiliation(s)
- Christine Reusch
- Applied Zoology and Nature Conservation, Zoological Inst. and Museum, Univ. of Greifswald Greifswald Germany
- Dept of Evolutionary Ecology, Leibniz Inst. for Zoo and Wildlife Research Berlin Germany
| | - Alexander Scheuerlein
- Applied Zoology and Nature Conservation, Zoological Inst. and Museum, Univ. of Greifswald Greifswald Germany
| | - Leo Grosche
- Applied Zoology and Nature Conservation, Zoological Inst. and Museum, Univ. of Greifswald Greifswald Germany
| | - Frauke Meier
- Applied Zoology and Nature Conservation, Zoological Inst. and Museum, Univ. of Greifswald Greifswald Germany
| | - Jutta Gampe
- Laboratory of Statistical Demography, Max‐Planck Inst. for Demographic Research Rostock Germany
| | - Melanie Dammhahn
- Behavioural Biology, Inst. for Neurobiology and Univ. of Münster Münster Germany
| | - Jaap van Schaik
- Applied Zoology and Nature Conservation, Zoological Inst. and Museum, Univ. of Greifswald Greifswald Germany
| | - Gerald Kerth
- Applied Zoology and Nature Conservation, Zoological Inst. and Museum, Univ. of Greifswald Greifswald Germany
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Gonnerman M, Shea SA, Sullivan K, Kamath P, Overturf K, Blomberg E. Dynamic winter weather moderates movement and resource selection of wild turkeys at high-latitude range limits. ECOLOGICAL APPLICATIONS : A PUBLICATION OF THE ECOLOGICAL SOCIETY OF AMERICA 2023; 33:e2734. [PMID: 36057107 DOI: 10.1002/eap.2734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 06/22/2022] [Accepted: 07/14/2022] [Indexed: 06/15/2023]
Abstract
For wide-ranging species in temperate environments, populations at high-latitude range limits are subject to more extreme conditions, colder temperatures, and greater snow accumulation compared with their core range. As climate change progresses, these bounding pressures may become more moderate on average, while extreme weather occurs more frequently. Individuals can mitigate temporarily extreme conditions by changing daily activity budgets and exhibiting plasticity in resource selection, both of which facilitate existence at and expansion of high-latitude range boundaries. However, relatively little work has explored how animals moderate movement and vary resource selection with changing weather, and a general framework for such investigations is lacking. We applied hidden Markov models and step selection functions to GPS data from wintering wild turkeys (Meleagris gallopavo) near their northern range limit to identify how weather influenced transition among discrete movement states, as well as state-specific resource selection. We found that turkeys were more likely to spend time in a stationary state as wind chill temperatures decreased and snow depth increased. Both stationary and roosting turkeys selected conifer forests and avoided land covers associated with foraging, such as agriculture and residential areas, while shifting their strength of selection for these features during poor weather. In contrast, mobile turkeys showed relatively weak resource selection, with less response in selection coefficients during poor weather. Our findings illustrate that behavioral plasticity in response to weather was context dependent, but movement behaviors most associated with poor weather were also those in which resource selection was most plastic. Given our results, the potential for wild turkey range expansion will partly be determined by the availability of habitat that allows them to withstand periodic inclement weather. Combining hidden Markov models with step selection functions is broadly applicable for evaluating plasticity in animal behavior and dynamic resource selection in response to changing weather. We studied turkeys at northern range limits, but this approach is applicable for any system expected to experience significant changes in the coming decade, and may be particularly relevant to populations existing at range peripheries.
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Affiliation(s)
- Matthew Gonnerman
- Department of Wildlife Fisheries and Conservation Biology, University of Maine, Orono, Maine, USA
| | - Stephanie A Shea
- School of Food and Agriculture, University of Maine, Orono, Maine, USA
| | - Kelsey Sullivan
- Maine Department of Inland Fisheries and Wildlife, Bangor, Maine, USA
| | - Pauline Kamath
- School of Food and Agriculture, University of Maine, Orono, Maine, USA
| | - Kaj Overturf
- Department of Wildlife Fisheries and Conservation Biology, University of Maine, Orono, Maine, USA
| | - Erik Blomberg
- Department of Wildlife Fisheries and Conservation Biology, University of Maine, Orono, Maine, USA
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48
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Kyo S, Murata K, Kawatou M, Minatoya K, Sunagawa GA, Masumoto H. Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest. JTCVS OPEN 2022; 12:201-210. [PMID: 36590714 PMCID: PMC9801336 DOI: 10.1016/j.xjon.2022.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 10/27/2022] [Accepted: 10/31/2022] [Indexed: 11/10/2022]
Abstract
Objectives Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced hypometabolism [QIH]). Here, we investigated the efficacy of QIH for the amelioration of acute kidney injury in an experimental circulatory arrest using a transgenic mouse model. Methods We genetically prepared mice in which QIH can be conditionally induced (QIH-ready mice). Mice were divided into 4 groups (n = 6 for each): QIH-ready normothermia (QN), QIH-ready hypothermia (QH), control normothermia (CN), and control hypothermia (CH). After induction of QIH, left thoracotomy and descending aorta crossclamping were conducted. After reperfusion, we collected kidneys and evaluated histologic changes and serum biochemical markers, specifically neutrophil gelatinase-associated lipocalin and cystatin C, indicating early kidney injury. Results Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH [P = .0021] and CN vs CH [P < .001]). QN exhibited lower neutrophil gelatinase-associated lipocalin and cystatin C levels than those in CN (neutrophil gelatinase-associated lipocalin: CN vs QN: 1.51 ± 0.71 vs 0.82 ± 0.32; P = .0414 and cystatin C: 1.48 ± 0.39 vs 0.71 ± 0.26; P = .0015). There was no significant difference between QN and QH. Conclusions QIH partly ameliorated acute kidney injury in a mouse ischemia model even in normothermia. QIH might be a promising approach to achieving sufficient kidney protection without hypothermic circulatory arrest in the future.
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Key Words
- AAV8, adeno-associated virus 8
- AKI, acute kidney injury
- CH, control hypothermia
- CN, control normothermia
- CNO, clozapine-N-oxide
- DHCA, deep hypothermic circulatory arrest
- NGAL, neutrophil gelatinase-associated lipocalin
- Q neurons, quiescence-inducing neurons
- Q neurons-induced hypometabolism
- QH, quiescence-inducing neurons-induced hypometabolism-ready hypothermia
- QIH, quiescence-inducing neurons-induced hypometabolism
- QN, quiescence-inducing neurons-induced hypometabolism-ready normothermia
- QRFP, pyroglutamylated RFamide peptide
- TA, ambient temperature
- TB, body temperature
- Vo2, the rate of oxygen consumption
- acute kidney injury
- circulatory arrest
- hibernation
- iCre, codon-improved Cre recombinase
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Affiliation(s)
- Shoichi Kyo
- Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kozue Murata
- Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
- Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Masahide Kawatou
- Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kenji Minatoya
- Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Genshiro A. Sunagawa
- Laboratory for Molecular Biology of Aging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
- Laboratory for Hibernation Biology, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Hidetoshi Masumoto
- Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
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Du X, Hu Y, Huang G, Wei F. The metabolic adaptation in wild vertebrates via omics approaches. LIFE METABOLISM 2022; 1:234-241. [PMID: 39872075 PMCID: PMC11749369 DOI: 10.1093/lifemeta/loac040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 11/27/2022] [Accepted: 12/23/2022] [Indexed: 01/29/2025]
Abstract
Metabolism is the basis for sustaining life and essential to the adaptive evolution of organisms. With the development of high-throughput sequencing technology, genetic mechanisms of adaptive evolution, including metabolic adaptation, have been extensively resolved by omics approaches, but a deep understanding of genetic and epigenetic metabolic adaptation is still lacking. Exploring metabolic adaptations from genetic and epigenetic perspectives in wild vertebrates is vital to understanding species evolution, especially for the early stages of adaptative evolution. Herein, we summarize the advances in our understanding of metabolic adaptations via omics approaches in wild vertebrates based on three types of cases: extreme environment, periodically changing environment, and changes of species characteristics. We conclude that the understanding of the formation of metabolic adaptations at the genetic level alone can well identify the adaptive genetic variation that has developed during evolution, but cannot resolve the potential impact of metabolic adaptations on the adaptative evolution in the future. Thus, it seems imperative to include epigenomics and metabolomics in the study of adaptation, and that in the future genomic and epigenetic data should be integrated to understand the formation of metabolic adaptation of wild vertebrate organisms.
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Affiliation(s)
- Xin Du
- Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yisi Hu
- Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, Guangdong 511458, China
| | - Guangping Huang
- Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
| | - Fuwen Wei
- Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, Guangdong 511458, China
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50
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Takahashi TM, Hirano A, Kanda T, Saito VM, Ashitomi H, Tanaka KZ, Yokoshiki Y, Masuda K, Yanagisawa M, Vogt KE, Tokuda T, Sakurai T. Optogenetic induction of hibernation-like state with modified human Opsin4 in mice. CELL REPORTS METHODS 2022; 2:100336. [PMID: 36452866 PMCID: PMC9701604 DOI: 10.1016/j.crmeth.2022.100336] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 09/01/2022] [Accepted: 10/19/2022] [Indexed: 05/28/2023]
Abstract
We recently determined that the excitatory manipulation of Qrfp-expressing neurons in the preoptic area of the hypothalamus (quiescence-inducing neurons [Q neurons]) induced a hibernation-like hypothermic/hypometabolic state (QIH) in mice. To control the QIH with a higher time resolution, we develop an optogenetic method using modified human opsin4 (OPN4; also known as melanopsin), a G protein-coupled-receptor-type blue-light photoreceptor. C-terminally truncated OPN4 (OPN4dC) stably and reproducibly induces QIH for at least 24 h by illumination with low-power light (3 μW, 473 nm laser) with high temporal resolution. The high sensitivity of OPN4dC allows us to transcranially stimulate Q neurons with blue-light-emitting diodes and non-invasively induce the QIH. OPN4dC-mediated QIH recapitulates the kinetics of the physiological changes observed in natural hibernation, revealing that Q neurons concurrently contribute to thermoregulation and cardiovascular function. This optogenetic method may facilitate identification of the neural mechanisms underlying long-term dormancy states such as sleep, daily torpor, and hibernation.
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Affiliation(s)
- Tohru M. Takahashi
- Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- International Integrative Institute for Sleep medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan
| | - Arisa Hirano
- Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- International Integrative Institute for Sleep medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan
- JST PRESTO, Japan
| | - Takeshi Kanda
- International Integrative Institute for Sleep medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan
| | - Viviane M. Saito
- Memory Research Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Okinawa, Japan
| | - Hiroto Ashitomi
- Memory Research Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Okinawa, Japan
| | - Kazumasa Z. Tanaka
- Memory Research Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Okinawa, Japan
| | - Yasufumi Yokoshiki
- Institute of Innovative Research (IIR), Tokyo Institute of Technology, Tokyo, Japan
| | - Kosaku Masuda
- Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- International Integrative Institute for Sleep medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan
| | - Masashi Yanagisawa
- International Integrative Institute for Sleep medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan
| | - Kaspar E. Vogt
- International Integrative Institute for Sleep medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan
| | - Takashi Tokuda
- JST PRESTO, Japan
- Institute of Innovative Research (IIR), Tokyo Institute of Technology, Tokyo, Japan
| | - Takeshi Sakurai
- Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- International Integrative Institute for Sleep medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan
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