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Tleiss F, Montanari M, Milleville R, Pierre O, Royet J, Osman D, Gallet A, Kurz CL. Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae. eLife 2024; 13:RP98716. [PMID: 39576741 PMCID: PMC11584180 DOI: 10.7554/elife.98716] [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: 11/24/2024] Open
Abstract
Multiple gut antimicrobial mechanisms are coordinated in space and time to efficiently fight foodborne pathogens. In Drosophila melanogaster, production of reactive oxygen species (ROS) and antimicrobial peptides (AMPs) together with intestinal cell renewal play a key role in eliminating gut microbes. A complementary mechanism would be to isolate and treat pathogenic bacteria while allowing colonization by commensals. Using real-time imaging to follow the fate of ingested bacteria, we demonstrate that while commensal Lactiplantibacillus plantarum freely circulate within the intestinal lumen, pathogenic strains such as Erwinia carotovora or Bacillus thuringiensis, are blocked in the anterior midgut where they are rapidly eliminated by antimicrobial peptides. This sequestration of pathogenic bacteria in the anterior midgut requires the Duox enzyme in enterocytes, and both TrpA1 and Dh31 in enteroendocrine cells. Supplementing larval food with hCGRP, the human homolog of Dh31, is sufficient to block the bacteria, suggesting the existence of a conserved mechanism. While the immune deficiency (IMD) pathway is essential for eliminating the trapped bacteria, it is dispensable for the blockage. Genetic manipulations impairing bacterial compartmentalization result in abnormal colonization of posterior midgut regions by pathogenic bacteria. Despite a functional IMD pathway, this ectopic colonization leads to bacterial proliferation and larval death, demonstrating the critical role of bacteria anterior sequestration in larval defense. Our study reveals a temporal orchestration during which pathogenic bacteria, but not innocuous, are confined in the anterior part of the midgut in which they are eliminated in an IMD-pathway-dependent manner.
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Affiliation(s)
- Fatima Tleiss
- Université Côte d'Azur, CNRS, INRAE, ISA, Nice, France
| | | | | | | | - Julien Royet
- Aix-Marseille Université, CNRS, IBDM, Marseille, France
| | - Dani Osman
- UMR PIMIT (Processus Infectieux en Milieu Insulaire Tropical) CNRS 9192-INSERM 1187-IRD 249-Université de La Réunion, île de La Réunion, France
| | - Armel Gallet
- Université Côte d'Azur, CNRS, INRAE, ISA, Nice, France
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2
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Abdalla MMI. Enteric neuropathy in diabetes: Implications for gastrointestinal function. World J Gastroenterol 2024; 30:2852-2865. [PMID: 38947292 PMCID: PMC11212710 DOI: 10.3748/wjg.v30.i22.2852] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 05/04/2024] [Accepted: 05/21/2024] [Indexed: 06/05/2024] Open
Abstract
Diabetes, commonly known for its metabolic effects, also critically affects the enteric nervous system (ENS), which is essential in regulating gastrointestinal (GI) motility, secretion, and absorption. The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions, such as gastroparesis and irregular bowel habits, primarily due to disruptions in the function of neuronal and glial cells within the ENS, as well as oxidative stress and inflammation. This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients. Additionally, it discusses the latest advances in diagnostic approaches, emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals. The editorial also reviews current and emerging therapeutic strategies, focusing on pharmacological treatments, dietary management, and potential neuromodulatory interventions. Ultimately, this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes, aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
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3
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Kokabi F, Ebrahimi S, Mirzavi F, Ghiasi Nooghabi N, Hashemi SF, Hashemy SI. The neuropeptide substance P/neurokinin-1 receptor system and diabetes: From mechanism to therapy. Biofactors 2023. [PMID: 36651605 DOI: 10.1002/biof.1935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 12/22/2022] [Indexed: 01/19/2023]
Abstract
Diabetes is a significant public health issue known as the world's fastest-growing disease condition. It is characterized by persistent hyperglycemia and subsequent chronic complications leading to organ dysfunction and, ultimately, the failure of target organs. Substance P (SP) is an undecapeptide that belongs to the family of tachykinin (TK) peptides. The SP-mediated activation of the neurokinin 1 receptor (NK1R) regulates many pathophysiological processes in the body. There is also a relation between the SP/NK1R system and diabetic processes. Importantly, deregulated expression of SP has been reported in diabetes and diabetes-associated chronic complications. SP can induce both diabetogenic and antidiabetogenic effects and thus affect the pathology of diabetes destructively or protectively. Here, we review the current knowledge of the functional relevance of the SP/NK1R system in diabetes pathogenesis and its exploitation for diabetes therapy. A comprehensive understanding of the role of the SP/NK1R system in diabetes is expected to shed further light on developing new therapeutic possibilities for diabetes and its associated chronic conditions.
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Affiliation(s)
- Fariba Kokabi
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Safieh Ebrahimi
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farshad Mirzavi
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | | | | | - Seyed Isaac Hashemy
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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4
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Effect of Chemically-Induced Diabetes Mellitus on Phenotypic Variability of the Enteric Neurons in the Descending Colon in the Pig. ANNALS OF ANIMAL SCIENCE 2021. [DOI: 10.2478/aoas-2020-0121] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Abstract
Gastrointestinal neuropathy in diabetes is one of numerous diseases resulting in abnormal functioning of the gastrointestinal tract (GIT), and it may affect any section of the GIT, including the descending colon. In the gastrointestinal system, the neurons are arranged in an interconnecting network defined as the enteric nervous system (ENS) which includes the myenteric plexus and the submucosal plexuses: inner and outer. Regular functioning of the ENS is determined by normal synthesis of the neurotransmitters and neuromodulators. This paper demonstrates the effect of hyperglycaemia on the number of enteric neurons which are immunoreactive to: neural isoform of nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), galanin (GAL), calcitonin generelated peptide (CGRP) and cocaine amphetamine-regulated transcript (CART) in the porcine descending colon. It was demonstrated that there was a statistically significant increase in the number of neurons within the myenteric plexus immunoreactive to all investigated substances. In the outer submucosal plexus, the CART-positive neurons were the only ones not to change, whereas no changes were recorded for nNOS or CART in the inner submucosal plexus. This study is the first study to discuss quantitative changes in the neurons immunoreactive to nNOS, VIP, GAL, CGRP and CART in the descending colon in diabetic pigs.
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Abstract
This paper is the forty-first consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2018 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (2), the roles of these opioid peptides and receptors in pain and analgesia in animals (3) and humans (4), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (5), opioid peptide and receptor involvement in tolerance and dependence (6), stress and social status (7), learning and memory (8), eating and drinking (9), drug abuse and alcohol (10), sexual activity and hormones, pregnancy, development and endocrinology (11), mental illness and mood (12), seizures and neurologic disorders (13), electrical-related activity and neurophysiology (14), general activity and locomotion (15), gastrointestinal, renal and hepatic functions (16), cardiovascular responses (17), respiration and thermoregulation (18), and immunological responses (19).
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Affiliation(s)
- Richard J Bodnar
- Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, City University of New York, Flushing, NY, 11367, United States.
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6
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Gonkowski S, Gajęcka M, Makowska K. Mycotoxins and the Enteric Nervous System. Toxins (Basel) 2020; 12:toxins12070461. [PMID: 32707706 PMCID: PMC7404981 DOI: 10.3390/toxins12070461] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/16/2020] [Accepted: 07/17/2020] [Indexed: 12/14/2022] Open
Abstract
Mycotoxins are secondary metabolites produced by various fungal species. They are commonly found in a wide range of agricultural products. Mycotoxins contained in food enter living organisms and may have harmful effects on many internal organs and systems. The gastrointestinal tract, which first comes into contact with mycotoxins present in food, is particularly vulnerable to the harmful effects of these toxins. One of the lesser-known aspects of the impact of mycotoxins on the gastrointestinal tract is the influence of these substances on gastrointestinal innervation. Therefore, the present study is the first review of current knowledge concerning the influence of mycotoxins on the enteric nervous system, which plays an important role, not only in almost all regulatory processes within the gastrointestinal tract, but also in adaptive and protective reactions in response to pathological and toxic factors in food.
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Affiliation(s)
- Sławomir Gonkowski
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-957 Olsztyn, Poland;
| | - Magdalena Gajęcka
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego Str. 13, 10-718 Olsztyn, Poland;
| | - Krystyna Makowska
- Department of Clinical Diagnostics, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 14, 10-957 Olsztyn, Poland
- Correspondence:
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Neurochemical Plasticity of nNOS-, VIP- and CART-Immunoreactive Neurons Following Prolonged Acetylsalicylic Acid Supplementation in the Porcine Jejunum. Int J Mol Sci 2020; 21:ijms21062157. [PMID: 32245119 PMCID: PMC7139762 DOI: 10.3390/ijms21062157] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 03/04/2020] [Accepted: 03/13/2020] [Indexed: 12/13/2022] Open
Abstract
Aspirin, also known as acetylsalicylic acid (ASA), is a commonly used anti-inflammatory drug that has analgesic and antipyretic properties. The side effects are well known, however, knowledge concerning its influence on gastric and intestinal innervation is limited. The enteric nervous system (ENS) innervates the whole gastrointestinal tract (GIT) and is comprised of more than one hundred million neurons. The capacity of neurons to adapt to microenvironmental influences, termed as an enteric neuronal plasticity, is an essential adaptive response to various pathological stimuli. Therefore, the goal of the present study was to determine the influence of prolonged ASA supplementation on the immunolocalization of neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP) and cocaine- and amphetamine- regulated transcript peptide (CART) in the porcine jejunum. The experiment was performed on 8 Pietrain × Duroc immature gilts. Using routine double-labelling immunofluorescence, we revealed that the ENS nerve cells underwent adaptive changes in response to the induced inflammation, which was manifested by upregulated or downregulated expression of the studied neurotransmitters. Our results suggest the participation of nNOS, VIP and CART in the development of inflammation and may form the basis for further neuro-gastroenterological research.
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Bulc M, Całka J, Palus K. Effect of Streptozotocin-Inducted Diabetes on the Pathophysiology of Enteric Neurons in the Small Intestine Based on the Porcine Diabetes Model. Int J Mol Sci 2020; 21:E2047. [PMID: 32192078 PMCID: PMC7139978 DOI: 10.3390/ijms21062047] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/13/2020] [Accepted: 03/14/2020] [Indexed: 12/31/2022] Open
Abstract
Hyperglycemia is one of the main causes of diabetes complications. Gastrointestinal (GI) disturbances are one of the most frequent complications during diabetes. The porcine digestive tract possesses physiological and pathological similarities to the human digestive tract. This also applies to the innervation of the gastrointestinal tract. In this study, the influence of experimentally-inducted hyperglycemia was examined on the expression of vesicular acetylcholine transporter (VAChT), cocaine- and amphetamine-regulated transcript (CART), galanin (GAL), vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP) in the enteric nervous system (ENS) neurons in the small intestine of the pig. During the current study, an increased number of neurons containing CART, VIP, GAL, and CGRP under streptozotocin injection were observed. The augmentation of expression included all enteric plexuses present in the small intestine. The same results were obtained in the case of VAChT; namely, chronic hyperglycemia led to an increase in the number of neurons utilizing VAChT in all investigated plexuses. The obtained results suggested that the function of neuropeptides studied in this experiment depended on their localization in the ENS structures, as well as part of the GI tract. Diabetes led to alterations in the neurochemical phenotype of small intestine enteric neurons.
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Affiliation(s)
- Michał Bulc
- Department of Clinical Physiology Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Str. 13, 10-719 Olsztyn, Poland; (J.C.); (K.P.)
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The Influence of a Hyperglycemic Condition on the Population of Somatostatin Enteric Neurons in the Porcine Gastrointestinal Tract. Animals (Basel) 2020; 10:ani10010142. [PMID: 31952333 PMCID: PMC7022948 DOI: 10.3390/ani10010142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 01/09/2020] [Accepted: 01/11/2020] [Indexed: 12/20/2022] Open
Abstract
Somatostatin (SOM) is the most common agent in the gastrointestinal (GI) tract that is involved in the regulation of several gastric functions, as well as in gastric disorders. Hyperglycemia, which develops as a consequence of improperly treated diabetes, can cause numerous disturbances in the appropriate functioning of the gastrointestinal tract. High glucose level is toxic to neurons. One of the lines of defense of neurons against this glucotoxicity are changes in their chemical coding. To better understood the role of SOM secreted by enteric neurons in neuronal response on elevated glucose level, pancreatic β cells were destroyed using streptozotocin. Due to the close similarity of the pig to humans, especially the GI tract, the current study used pigs as an animal model. The results revealed that the number of enteric neurons immunoreactive to SOM (SOM-IR) in a physiological state clearly depend on the part of the GI tract studied. In turn, experimentally induced diabetes caused changes in the number of SOM-IR neurons. The least visible changes were observed in the stomach, where an increase in SOM-IR neurons was observed, only in the submucosal plexus in the corpus. However, diabetes led to an increase in the population of myenteric and submucosal neurons immunoreactive to SOM in all segments of the small intestine. The opposite situation occurred in the descending colon, where a decrease in the number of SOM-IR neurons was visible. This study underlines the significant role of SOM expressed in enteric nervous system neurons during diabetes.
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11
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Czajkowska M, Rychlik A, Całka J. Long-term treatment with naproxen changes the chemical coding of the porcine intramural duodenum neurons. Ann Anat 2019; 227:151425. [PMID: 31610253 DOI: 10.1016/j.aanat.2019.151425] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 07/25/2019] [Accepted: 09/20/2019] [Indexed: 12/22/2022]
Abstract
Due to numerous therapeutic applications and high availability, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs worldwide. However, long-term use of these drugs can lead to damage to the gastrointestinal mucosa. The enteric nervous system (ENS), which is part of the autonomic nervous system, controls most aspects of gastrointestinal activity. Enteric neurons are characterized by considerable chemical plasticity and the appearance of a pathological factor results in a change in the synthesis of neurotransmitters. The purpose of this study was to determine the effects of naproxen on expression of biologically active substances by intramural neurons supplying the porcine duodenum. The study was performed on eight immature pigs of the Pietrain x Duroc race (approximately 20kg of body weight). The animals were divided into two groups - a control (C group) and an experimental group (N group). Group C (n=4) consisted of animals which received empty gelatine capsules. Group N (n=4) was composed of pigs who received naproxen orally for 28 days, approximately one hour before feeding. After this time, animals from both groups were euthanized. Frozen sections (14μm thickness) were then prepared from the collected duodenum and subjected to double immunofluorescence staining. Antibodies against the neuronal marker PGP 9.5 and against vasoactive intestinal polypeptide (VIP), substance P (SP), neuronal nitric oxide synthase (nNOS), galanin (GAL), pituitary adenylate cyclase-activating polypeptide (PACAP) and cocaine- and amphetamine- regulated transcript peptide (CART) were used as primary antibodies. The polyclonal donkey anti-rabbit, anti-mouse and anti-guinea pig IgG antibodies - Alexa Fluor 488 and 546 - were also used for staining. Analysis of the results obtained with a fluorescence microscope showed a significant increase in the number of nNOS-, VIP-, GAL-, PACAP- and CART-immunoreactive ganglionated neurons and a decrease in the number of SP-positive neurons in the myenteric and submucosal plexuses of the porcine duodenum. The obtained results indicate the participation of enteric neurotransmitters in the neuronal duodenal response to naproxen-induced inflammation.
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Affiliation(s)
- Marta Czajkowska
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Str. 13, Olsztyn, 10-718, Poland.
| | - Andrzej Rychlik
- Department of Clinical Diagnostics, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Str. 14, Olsztyn, 10-957, Poland
| | - Jarosław Całka
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Str. 13, Olsztyn, 10-718, Poland
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12
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Meldgaard T, Keller J, Olesen AE, Olesen SS, Krogh K, Borre M, Farmer A, Brock B, Brock C, Drewes AM. Pathophysiology and management of diabetic gastroenteropathy. Therap Adv Gastroenterol 2019; 12:1756284819852047. [PMID: 31244895 PMCID: PMC6580709 DOI: 10.1177/1756284819852047] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 04/26/2019] [Indexed: 02/04/2023] Open
Abstract
Polyneuropathy is a common complication to diabetes. Neuropathies within the enteric nervous system are associated with gastroenteropathy and marked symptoms that severely reduce quality of life. Symptoms are pleomorphic but include nausea, vomiting, dysphagia, dyspepsia, pain, bloating, diarrhoea, constipation and faecal incontinence. The aims of this review are fourfold. First, to provide a summary of the pathophysiology underlying diabetic gastroenteropathy. Secondly to give an overview of the diagnostic methods. Thirdly, to provide clinicians with a focussed overview of current and future methods for pharmacological and nonpharmacological treatment modalities. Pharmacological management is categorised according to symptoms arising from the upper or lower gut as well as sensory dysfunctions. Dietary management is central to improvement of symptoms and is discussed in detail, and neuromodulatory treatment modalities and other emerging management strategies for diabetic gastroenteropathy are discussed. Finally, we propose a diagnostic/investigation algorithm that can be used to support multidisciplinary management.
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Affiliation(s)
| | - Jutta Keller
- Israelitic Hospital in Hamburg, Academic
Hospital University of Hamburg, Germany
| | - Anne Estrup Olesen
- Mech-Sense, Department of Gastroenterology and
Hepatology and Department of Clinical Medicine, Aalborg University Hospital,
Denmark,Department of Clinical Medicine, Aalborg
University, Denmark
| | - Søren Schou Olesen
- Mech-Sense, Department of Gastroenterology and
Hepatology and Department of Clinical Medicine, Aalborg University Hospital,
Denmark,Department of Clinical Medicine, Aalborg
University, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology,
Aarhus University Hospital, Denmark
| | - Mette Borre
- Department of Hepatology and Gastroenterology,
Aarhus University Hospital, Denmark
| | - Adam Farmer
- Department of Gastroenterology, University
Hospitals of North Midlands, Stoke on Trent, Staffordshire, UK,Centre for Digestive Diseases, Blizard
Institute of Cell and Molecular Science, Wingate Institute of
Neurogastroenterology, Barts and the London School of Medicine and
Dentistry, Queen Mary University of London, UK
| | - Birgitte Brock
- Department of Clinical Research, Steno Diabetes
Center Copenhagen (SDCC), Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and
Hepatology and Department of Clinical Medicine, Aalborg University Hospital,
Denmark,Department of Clinical Medicine, Aalborg
University, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and
Hepatology and Department of Clinical Medicine, Aalborg University Hospital,
Denmark,Department of Clinical Medicine, Aalborg
University, Denmark
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Bulc M, Palus K, Dąbrowski M, Całka J. Hyperglycaemia-Induced Downregulation in Expression of nNOS Intramural Neurons of the Small Intestine in the Pig. Int J Mol Sci 2019; 20:ijms20071681. [PMID: 30987291 PMCID: PMC6480956 DOI: 10.3390/ijms20071681] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 04/01/2019] [Accepted: 04/02/2019] [Indexed: 12/22/2022] Open
Abstract
Diabetic autonomic peripheral neuropathy (PN) involves a broad spectrum of organs. One of them is the gastrointestinal (GI) tract. The molecular mechanisms underlying the pathogenesis of digestive complications are not yet fully understood. Digestion is controlled by the central nervous system (CNS) and the enteric nervous system (ENS) within the wall of the GI tract. Enteric neurons exert regulatory effects due to the many biologically active substances secreted and released by enteric nervous system (ENS) structures. These include nitric oxide (NO), produced by the neural nitric oxide synthase enzyme (nNOS). It is a very important inhibitory factor, necessary for smooth muscle relaxation. Moreover, it was noted that nitrergic innervation can undergo adaptive changes during pathological processes. Additionally, nitrergic neurons function may be regulated through the synthesis of other active neuropeptides. Therefore, in the present study, using the immunofluorescence technique, we first examined the influence of hyperglycemia on the NOS- containing neurons in the porcine small intestine and secondly the co-localization of nNOS with vasoactive intestinal polypeptide (VIP), galanin (GAL) and substance P (SP) in all plexuses studied. Following chronic hyperglycaemia, we observed a reduction in the number of the NOS-positive neurons in all intestinal segments studied, as well as an increased in investigated substances in nNOS positive neurons. This observation confirmed that diabetic hyperglycaemia can cause changes in the neurochemical characteristics of enteric neurons, which can lead to numerous disturbances in gastrointestinal tract functions. Moreover, can be the basis of an elaboration of these peptides analogues utilized as therapeutic agents in the treatment of GI complications.
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Affiliation(s)
- Michał Bulc
- Department of Clinical Physiology Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Str. 13, 10-719 Olsztyn, Poland.
| | - Katarzyna Palus
- Department of Clinical Physiology Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Str. 13, 10-719 Olsztyn, Poland.
| | - Michał Dąbrowski
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego Str. 13, 10-719 Olsztyn, Poland.
| | - Jarosław Całka
- Department of Clinical Physiology Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Str. 13, 10-719 Olsztyn, Poland.
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