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Salem EM, Rizk H, Abouelela YS, Prince A, Tohamy AF, Lasheen NA, Ezzat BA, Mostafa S. Regenerative potentials of bone marrow mesenchymal stem cells derived exosomes or its combination with zinc in recovery of degenerated circumvallate papilla following surgical bilateral transection of glossopharyngeal nerve in rats. BMC Oral Health 2024; 24:1320. [PMID: 39478548 PMCID: PMC11523770 DOI: 10.1186/s12903-024-05050-7] [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: 06/13/2024] [Accepted: 10/14/2024] [Indexed: 11/02/2024] Open
Abstract
BACKGROUND Taste buds' innervation is necessary to sustain their cell turnover, differentiated taste buds and nerve fibers in circumvallate papilla (CVP) disappear following glossopharyngeal nerve transection. Normally, taste buds recover to baseline number in about 70 days. Bone marrow stem cell (BM-MSC) derived exosomes or their combination with Zinc chloride are used to assess their potential to speed up the regeneration process of CVP following bilateral deafferentation. METHODS Twenty-eight male Sprague-Dawley rats were randomly divided into four groups; Group I: subjected to sham operation followed by IP injection of saline. The other experimental groups (II, III and IV) were subjected to surgical bilateral transection of glossopharyngeal nerve. Group II received single IP injection of saline. Group III received single IV injection of BM-MSC-derived exosomes (100 µg). Group IV received single IV injection of BM-MSC-derived exosomes and single IP injection of zinc chloride (5 mg/kg). After 28 days, CVP was dissected and prepared for histological and histomorphometric analysis, RT-PCR for cytokeratin 8 gene expression, ELISA to assess protein level of brain-derived neurotrophic factor, redox state analysis of malondialdehyde and glutathione content, followed by statistical analysis. RESULTS Histopathologically, group II exhibited great tissue damage with marked reduction in taste buds and signs of degeneration in the remaining ones. Group III was close to control group with marked improvement in taste buds' number and structure. Group IV showed inferior results when compared to group III, with many immature taste buds and signs of degeneration. Statistical results showed that groups I and III have significantly higher values than groups II and IV regarding taste buds' number, cytokeratin 8, and reduced glutathione. However, malondialdehyde demonstrated high significant values in group IV compared to groups I and III. Regarding brain-derived neurotrophic factor, group III had significantly higher values than group II. CONCLUSION BM-MSC-derived exosomes have superior regenerative potentials in acceleration of CVP and nerve healing following bilateral transection of glossopharyngeal nerve in contrary to its combination with zinc chloride.
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Affiliation(s)
- Eman Mohamed Salem
- Oral Biology Department, College of Oral and Dental Surgery, Misr University for Science and Technology, Giza, 12568, Egypt.
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, 115533, Egypt.
| | - Hamdy Rizk
- Anatomy and Embryology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Yara S Abouelela
- Anatomy and Embryology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Abdelbary Prince
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Adel Fathy Tohamy
- Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Nawal A Lasheen
- Oral Biology Department, College of Oral and Dental Surgery, Misr University for Science and Technology, Giza, 12568, Egypt
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, 115533, Egypt
| | - Bassant A Ezzat
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, 115533, Egypt
| | - Sana Mostafa
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, 115533, Egypt
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Harada K, Miki K, Tanaka S, Kogo M, Wakisaka S. Lectin histochemistry of posterior lingual glands of developing rats. Sci Rep 2023; 13:10365. [PMID: 37365173 DOI: 10.1038/s41598-023-36154-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
The posterior lingual glands are classified as Weber and von Ebner glands. Glycans play an important role in salivary glands. Although the distribution of glycans can explain functional diversity and variation, there are many unknowns in the developing rat posterior lingual glands. The purpose of this study was to elucidate the relationship between the development and function of the posterior lingual gland in rats by histochemical analysis using lectins that bind to sugar residues. In adult rats, Arachis hypogaea (PNA), Glycine maximus (SBA), and Triticum vulgaris (WGA) were associated with serous cells and Dolichos biflorus (DBA) with mucous cells. In both Weber's and von Ebner's glands, all 4 lectins were bound to serous cells in early development, but as development progressed, DBA disappeared in serous cells and only the DBA remained in mucous cells. These results suggest that Galβ (1,3) > Galβ(1,4) > Gal, αGalNAc > αGal > βGalNAc, NeuAc > (GalNAc)2-3>>>GlcNAc, and GalNAcα(1,3) are present in the early stage of development, but that GalNAcα(1,3) disappear in serous cells and only GalNAcα(1,3) are localized in mucous cells after maturation. These results indicate that Weber glands function as serous glands in the early postnatal stage when von Ebner glands have not matured.
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Affiliation(s)
- Kazuma Harada
- The First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita, Japan.
| | - Koji Miki
- Department of Periodonology, Graduate School of Dentistry, Osaka University, Suita, Japan
| | - Susumu Tanaka
- The First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita, Japan
| | - Mikihiko Kogo
- The First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita, Japan
| | - Satoshi Wakisaka
- Department of Anatomy and Cell Biology, Graduate School of Dentistry, Osaka University, Suita, Japan
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Localization of BDNF and Calretinin in Olfactory Epithelium and Taste Buds of Zebrafish (Danio rerio). Int J Mol Sci 2022; 23:ijms23094696. [PMID: 35563087 PMCID: PMC9101965 DOI: 10.3390/ijms23094696] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/19/2022] [Accepted: 04/22/2022] [Indexed: 11/17/2022] Open
Abstract
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and it is involved in several fundamental functions in the central and peripheral nervous systems, and in sensory organs. BDNF regulates the chemosensory systems of mammals and is consistently expressed in those organs. In zebrafish, the key role of BDNF in the biology of the hair cells of the inner ear and lateral line system has recently been demonstrated. However, only some information is available about its occurrence in the olfactory epithelium, taste buds, and cutaneous isolated chemosensory cells. Therefore, this study was undertaken to analyze the involvement of BDNF in the chemosensory organs of zebrafish during the larval and adult stages. To identify cells displaying BDNF, we compared the cellular pattern of BDNF-displaying cells with those immunoreactive for calretinin and S100 protein. Our results demonstrate the localization of BDNF in the sensory part of the olfactory epithelium, mainly in the ciliated olfactory sensory neurons in larvae and adult zebrafish. Intense immunoreaction for BDNF was also observed in the chemosensory cells of oral and cutaneous taste buds. Moreover, a subpopulation of olfactory sensory neurons and chemosensory cells of olfactory rosette and taste bud, respectively, showed marked immunopositivity for calcium-binding protein S100 and calretinin. These results demonstrate the possible role of BDNF in the development and maintenance of olfactory sensory neurons and sensory cells in the olfactory epithelium and taste organs of zebrafish during all stages of development.
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Hino K, Hirashima S, Tsuneyoshi R, Togo A, Hiroshige T, Kusukawa J, Nakamura KI, Ohta K. Three-dimensional ultrastructure and histomorphology of mouse circumvallate papillary taste buds before and after birth using focused ion beam-scanning electron microscope tomography. Tissue Cell 2022; 75:101714. [DOI: 10.1016/j.tice.2021.101714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 10/19/2022]
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Aragona M, Porcino C, Guerrera MC, Montalbano G, Laurà R, Cometa M, Levanti M, Abbate F, Cobo T, Capitelli G, Vega JA, Germanà A. The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish. Int J Mol Sci 2022; 23:ijms23052621. [PMID: 35269763 PMCID: PMC8910639 DOI: 10.3390/ijms23052621] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/21/2022] [Accepted: 02/25/2022] [Indexed: 12/15/2022] Open
Abstract
The brain-derived neurotrophic factor (BDNF) was discovered in the last century, and identified as a member of the neurotrophin family. BDNF shares approximately 50% of its amino acid with other neurotrophins such as NGF, NT-3 and NT-4/5, and its linear amino acid sequences in zebrafish (Danio rerio) and human are 91% identical. BDNF functions can be mediated by two categories of receptors: p75NTR and Trk. Intriguingly, BDNF receptors were highly conserved in the process of evolution, as were the other NTs’ receptors. In this review, we update current knowledge about the distribution and functions of the BDNF-TrkB system in the sensory organs of zebrafish. In fish, particularly in zebrafish, the distribution and functions of BDNF and TrkB in the brain have been widely studied. Both components of the system, associated or segregated, are also present outside the central nervous system, especially in sensory organs including the inner ear, lateral line system, retina, taste buds and olfactory epithelium.
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Affiliation(s)
- Marialuisa Aragona
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
| | - Caterina Porcino
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
| | - Maria Cristina Guerrera
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
| | - Giuseppe Montalbano
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
| | - Rosaria Laurà
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
| | - Marzio Cometa
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
| | - Maria Levanti
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
| | - Francesco Abbate
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
| | - Teresa Cobo
- Departamento de Cirugía y Especialidades Médico-Quirúrgicas, Universidad de Oviedo, 33006 Oviedo, Spain;
| | - Gabriel Capitelli
- Faculty of Medical Sciences, University of Buenos Aires, Viamonte 1053, CABA, Buenos Aires 1056, Argentina;
| | - José A. Vega
- Grupo SINPOS, Universidad de Oviedo, 33003 Oviedo, Spain;
- Departamento de Morfología y Biología Celular, Universidad de Oviedo, 33006 Oviedo, Spain
- Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 7500912, Chile
| | - Antonino Germanà
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy; (M.A.); (C.P.); (M.C.G.); (G.M.); (R.L.); (M.C.); (M.L.); (F.A.)
- Correspondence:
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Kim JY, Kim TY, Lee ES, Aryal YP, Pokharel E, Sung S, Sohn WJ, Kim JY, Jung JK. Implications of the specific localization of YAP signaling on the epithelial patterning of circumvallate papilla. J Mol Histol 2021; 52:313-320. [PMID: 33420594 DOI: 10.1007/s10735-020-09951-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 12/26/2020] [Indexed: 11/24/2022]
Abstract
Circumvallate papilla (CVP) is a distinctively structured with dome-shaped apex, and the surrounding trench which contains over two hundred taste buds on the lateral walls. Although CVP was extensively studied to determine the regulatory mechanisms during organogenesis, it still remains to be elucidated the principle mechanisms of signaling regulations on morphogenesis including taste buds formation. The key role of Yes-associated protein (YAP) in the regulation of organ size and cell proliferation in vertebrates is well understood, but little is known about the role of this signaling pathway in CVP development. We aimed to determine the putative roles of YAP signaling in the epithelial patterning during CVP morphogenesis. To evaluate the precise localization patterns of YAP and other related signaling molecules, including β-catenin, Ki67, cytokeratins, and PGP9.5, in CVP tissue, histology and immunohistochemistry were employed at E16 and adult mice. Our results suggested that there are specific localization patterns of YAP and Wnt signaling molecules in developing and adult CVP. These concrete localization patterns would provide putative involvements of YAP and Wnt signaling for proper epithelial cell differentiation including the formation and maintenance of taste buds.
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Affiliation(s)
- Ji-Youn Kim
- Department of Dental Hygiene, Gachon University, Inchoen, Korea
| | - Tae-Young Kim
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, Korea
| | - Eui-Seon Lee
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, Korea
| | - Yam Prasad Aryal
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, Korea
| | - Elina Pokharel
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, Korea
| | - Shijin Sung
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, Korea
| | - Wern-Joo Sohn
- Pre-Major of Cosmetics and Pharmaceutics, Daegu Haany University, Gyeongsan, 38610, Korea
| | - Jae-Young Kim
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, Korea.
| | - Jae-Kwang Jung
- Department of Oral Medicine, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, Korea.
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Morphological study of the rabbit gustatory lingual papillae during postnatal life by light and scanning electron microscopy. Anat Sci Int 2020; 95:455-469. [PMID: 32323219 DOI: 10.1007/s12565-020-00542-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 04/10/2020] [Indexed: 12/21/2022]
Abstract
This study aimed to investigate the postnatal morphological features of rabbit's lingual gustatory papillae using histological, histochemical, morphometrical and scanning electron microscopical studies. A total of 48 New Zealand rabbits (1, 7, 15, 23, 30, 60 days postnatal) were used as the material. Tongue consisted of an apex, body and root with three types of gustatory papillae fungiform, vallate and foliate. Rounded to oval fungiform papillae were distributed on lingual apex among filiform papillae. Two foliate papillae on lateroposterior side have parallel folia increased progressively in number (14-20) with age advancement. Two oval vallate papillae on lingual root surrounded by annular grooves. Histologically, the gustatory papillary epithelium was thin at birth then increased in stratification and cornification from third to fourth week. Vallate and foliate grooves were shallow in newborns then grew deeply by desquamation of their lining epithelium which completely opened and connected with lingual excretory ducts at 23 days. Developing serous von Ebner's glands appeared at 23 days and became lobulated form 1-2 months. They gave a negative reaction with Periodic Acid Schiff-Alcian blue stain, while mucous Weber's glands showed Alcian blue positive reaction. Taste buds were firstly seen at 15 days old, increased in number and size and became mature with taste pores from third to fourth week. They distributed dorsally on fungiform and on lateral sides of vallate and foliate. This structural adaptation and maturity of gustatory papillae to meet the functional demands of food ingestion during the transition from suckling to dry matter feeding.
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Di YZ, Han BS, Di JM, Liu WY, Tang Q. Role of the brain-gut axis in gastrointestinal cancer. World J Clin Cases 2019; 7:1554-1570. [PMID: 31367615 PMCID: PMC6658366 DOI: 10.12998/wjcc.v7.i13.1554] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 04/04/2019] [Accepted: 05/02/2019] [Indexed: 02/05/2023] Open
Abstract
Several studies have largely focused on the significant role of the nervous and immune systems in the process of tumorigenesis, including tumor growth, proliferation, apoptosis, and metastasis. The brain-gut-axis is a new paradigm in neuroscience, which describes the biochemical signaling between the gastrointestinal (GI) tract and the central nervous system. This axis may play a critical role in the tumorigenesis and development of GI cancers. Mechanistically, the bidirectional signal transmission of the brain-gut-axis is complex and remains to be elucidated. In this article, we review the current findings concerning the relationship between the brain-gut axis and GI cancer cells, focusing on the significant role of the brain-gut axis in the processes of tumor proliferation, invasion, apoptosis, autophagy, and metastasis. It appears that the brain might modulate GI cancer by two pathways: the anatomical nerve pathway and the neuroendocrine route. The simulation and inactivation of the central nervous, sympathetic, and parasympathetic nervous systems, or changes in the innervation of the GI tract might contribute to a higher incidence of GI cancers. In addition, neurotransmitters and neurotrophic factors can produce stimulatory or inhibitory effects in the progression of GI cancers. Insights into these mechanisms may lead to the discovery of potential prognostic and therapeutic targets.
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Affiliation(s)
- Yang-Zi Di
- Department of General Surgery, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Bo-Sheng Han
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 443000, Hubei Province, China
| | - Jun-Mao Di
- Department of General Surgery, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Wei-Yan Liu
- Department of General Surgery, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Qiang Tang
- Department of General Surgery, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
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Haddad S, Noreldin AE, Kamal B, Abdeen A, Farouk SM, Abbott LC, Abdo M. Morphological and functional comparison of lingual papillae in suckling and adult feral cats: Forensic evidence. Anat Histol Embryol 2019; 48:404-414. [DOI: 10.1111/ahe.12460] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 05/06/2019] [Accepted: 06/04/2019] [Indexed: 11/30/2022]
Affiliation(s)
- Seham Haddad
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine University of Sadat City Sadat City Egypt
| | - Ahmed E. Noreldin
- Department of Histology and Cytology, Faculty of Veterinary Medicine Damanhour University Damanhour Egypt
| | - Basma Kamal
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine University of Sadat City Sadat City Egypt
| | - Ahmed Abdeen
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine Benha University Toukh Egypt
| | - Sameh M. Farouk
- Department of Cytology and Histology, Faculty of Veterinary Medicine Suez Canal University Ismailia Egypt
| | - Louise C. Abbott
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station TX USA
| | - Mohamed Abdo
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine University of Sadat City Sadat City Egypt
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Xu J, Lewandowski BC, Miyazawa T, Shoji Y, Yee K, Bryant BP. Spilanthol Enhances Sensitivity to Sodium in Mouse Taste Bud Cells. Chem Senses 2019; 44:91-103. [PMID: 30364996 PMCID: PMC6350677 DOI: 10.1093/chemse/bjy069] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Overconsumption of NaCl has been linked to increased hypertension-related morbidity. Compounds that can enhance NaCl responses in taste cells could help reduce human NaCl consumption without sacrificing perceived saltiness. Spilanthol is an unsaturated alkylamide isolated from the Jambu plant (Acmella oleracea) that can induce tingling, pungency, and numbing in the mouth. Structurally similar fatty acid amides, such as sanshool, elicit numbing and tingling sensations by inhibiting 2-pore-domain potassium leak channels on trigeminal sensory neurons. Even when insufficient to induce action potential firing, leak current inhibition causes depolarization and increased membrane resistance, which combine to make cells more sensitive to subsequent depolarizing stimuli, such as NaCl. Using calcium imaging, we tested whether spilanthol alters sensitivity to NaCl in isolated circumvallate taste bud cells and trigeminal sensory neurons of mice (Mus musculus). Micromolar spilanthol elicited little to no response in taste bud cells or trigeminal neurons. These same perithreshold concentrations of spilanthol significantly enhanced responses to NaCl (140 and 200 mM) in taste bud cells. Trigeminal neurons, however, exhibited response enhancement only at the highest concentrations of NaCl and spilanthol tested. Using a combination of potassium depolarization, immunohistochemistry, and Trpm5-GFP and Tas1r3-GFP mice to characterize taste bud cells by type, we found spilanthol enhancement of NaCl responses most prevalent in NaCl-responsive type III cells, and commonly observed in NaCl-responsive type II cells. Our results indicate that spilanthol enhances NaCl responses in taste bud cells and point to a family of compounds that may have utility as salty taste enhancers.
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Affiliation(s)
- Jiang Xu
- Monell Chemical Senses Center, Philadelphia, PA , USA
| | | | | | - Yasutaka Shoji
- Ogawa & Co. Ltd., Nihonbashi Honcho Chuo-ku, Tokyo, Japan
| | - Karen Yee
- Monell Chemical Senses Center, Philadelphia, PA , USA
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Immunohistochemical localization of Nox in mouse circumvallate papillae. Tissue Cell 2015; 47:550-8. [DOI: 10.1016/j.tice.2015.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 09/16/2015] [Accepted: 10/02/2015] [Indexed: 11/19/2022]
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Meng L, Jiang X, Ji R. Role of neurotrophin in the taste system following gustatory nerve injury. Metab Brain Dis 2015; 30:605-13. [PMID: 25381474 DOI: 10.1007/s11011-014-9626-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Accepted: 10/30/2014] [Indexed: 12/12/2022]
Abstract
Taste system is a perfect system to study degeneration and regeneration after nerve injury because the taste system is highly plastic and the regeneration is robust. Besides, degeneration and regeneration can be easily measured since taste buds arise in discrete locations, and nerves that innervate them can be accurately quantified. Neurotrophins are a family of proteins that regulate neural survival, function, and plasticity after nerve injury. Recent studies have shown that neurotrophins play an important role in the developmental and mature taste system, indicating neurtrophin might also regulate taste system following gustatory nerve injury. This review will summarize how taste system degenerates and regenerates after gustatory nerve cut and conclude potential roles of neurotrophin in regulating the process.
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Affiliation(s)
- Lingbin Meng
- Department of Anatomical Sciences and Neurobiology, University of Louisville, School of Medicine, Louisville, KY, 40202, USA
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Wang R, van Keeken NMA, Siddiqui S, Dijksman LM, Maudsley S, Derval D, van Dam PS, Martin B. Higher TNF-α, IGF-1, and Leptin Levels are Found in Tasters than Non-Tasters. Front Endocrinol (Lausanne) 2014; 5:125. [PMID: 25120532 PMCID: PMC4114300 DOI: 10.3389/fendo.2014.00125] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Accepted: 07/11/2014] [Indexed: 12/03/2022] Open
Abstract
Taste perception is controlled by taste cells that are present in the tongue that produce and secrete various metabolic hormones. Recent studies have demonstrated that taste receptors in tongue, gut, and pancreas are associated with local hormone secretion. The aim of this study was to determine whether there is a link between taste sensitivity and levels of circulating metabolic hormones in humans and whether taste sensitivity is potentially related to peripheral metabolic regulation. Thirty-one subjects were recruited and separated into tasters and non-tasters based on their phenol thiocarbamide (PTC) bitter taste test results. Fasting plasma and saliva were collected and levels of hormones and cytokines were assayed. We observed significant differences in both hormone levels and hormone-body mass index (BMI) correlation between tasters and non-tasters. Tasters had higher plasma levels of leptin (p = 0.05), tumor necrosis factor-α (TNF-α) (p = 0.04), and insulin-like growth factor 1 (IGF-1) (p = 0.03). There was also a trend toward increased IGF-1 levels in the saliva of tasters (p = 0.06). We found a positive correlation between plasma levels of glucose and BMI (R = 0.4999, p = 0.04) exclusively in non-tasters. In contrast, plasma C-peptide levels were found to be positively correlated to BMI (R = 0.5563, p = 0.03) in tasters. Saliva TNF-α levels were negatively correlated with BMI in tasters (R = -0.5908, p = 0.03). Our findings demonstrate that there are differences in circulating levels of leptin, TNF-α, and IGF-1 between tasters and non-tasters. These findings indicate that in addition to the regulation of food consumption, taste perception also appears to be tightly linked to circulating metabolic hormone levels. People with different taste sensitivity may respond differently to the nutrient stimulation. Further work investigating the link between taste perception and peripheral metabolic control could potentially lead to the development of novel therapies for obesity or Type 2 diabetes.
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Affiliation(s)
- Rui Wang
- Metabolism Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
| | | | - Sana Siddiqui
- Receptor Pharmacology Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
| | - Lea M. Dijksman
- Teaching Hospital, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
| | - Stuart Maudsley
- Receptor Pharmacology Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
- VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium
| | - Diana Derval
- Better Immune System Foundation, Amsterdam, Netherlands
| | - P. Sytze van Dam
- Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
| | - Bronwen Martin
- Metabolism Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
- *Correspondence: Bronwen Martin, Metabolism Unit, National Institute on Aging, 251 Bayview Blvd., Suite 100 Room 08C009, Baltimore, MD 21224, USA e-mail:
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Frias B, Lopes T, Pinto R, Cruz F, Cruz CD. Neurotrophins in the lower urinary tract: becoming of age. Curr Neuropharmacol 2012; 9:553-8. [PMID: 22654715 PMCID: PMC3263451 DOI: 10.2174/157015911798376253] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2010] [Revised: 07/19/2010] [Accepted: 07/19/2010] [Indexed: 01/23/2023] Open
Abstract
The lower urinary tract (LUT) comprises a storage unit, the urinary bladder, and an outlet, the urethra. The coordination between the two structures is tightly controlled by the nervous system and, therefore, LUT function is highly susceptible to injuries to the neuronal pathways involved in micturition control. These injuries may include lesions to the
spinal cord or to nerve fibres and result in micturition dysfunction. A common trait of micturition pathologies, irrespective of its origin, is an upregulation in synthesis and secretion of neurotrophins, most notably Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF). These neurotrophins are produced by neuronal and non-neuronal cells and exert their effects upon binding to their high-affinity receptors abundantly expressed in the neuronal circuits regulating
LUT function. In addition, NGF and BDNF are present in detectable amounts in the urine of patients suffering from various LUT pathologies, suggesting that analysis of urinary NGF and BDNF may serve as likely biomarkers to be studied in tandem with other factors when diagnosing patients. Studies with experimental models of bladder dysfunction
using antagonists of NGF and BDNF receptors as well as scavenging agents suggest that those NTs may be key elements in the pathophysiology of bladder dysfunctions. In addition, available data indicates that NGF and BDNF might constitute future targets for designing new drugs for better treatment of bladder dysfunction.
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Affiliation(s)
- Bárbara Frias
- Department of Experimental Biology, Faculty of Medicine of Porto, Alameda Hernâni Monteiro, 4200-319 Porto, Portugal
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Iwasaki SI, Aoyagi H, Asami T, Wanichanon C, Jackowiak H. Patterns of immunoreactivity specific for gustducin and for NCAM differ in developing rat circumvallate papillae and their taste buds. Acta Histochem 2012; 114:259-69. [PMID: 21703667 DOI: 10.1016/j.acthis.2011.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2011] [Revised: 05/24/2011] [Accepted: 05/30/2011] [Indexed: 10/18/2022]
Abstract
α-Gustducin and neural cell adhesion molecule (NCAM) are molecules previously found to be expressed in different cell types of mammalian taste buds. We examined the expression of α-gustducin and NCAM during the morphogenesis of circumvallate papillae and the formation of their taste buds by immunofluorescence staining and laser-scanning microscopy of semi-ultrathin sections of fetal and juvenile rat tongues. Images obtained by confocal laser scanning microscopy in transmission mode were also examined to provide outlines of histology and cell morphology. Morphogenesis of circumvallate papillae had already started on embryonic day 13 (E13) and was evident as the formation of placode. By contrast, taste buds in the circumvallate papillae started to appear between postnatal day 0 (P0) and P7. Although no cells with immunoreactivity specific for α-gustducin were detected in fetuses from E13 to E19, cells with NCAM-specific immunoreactivity were clearly apparent in the entire epithelium of the circumvallate papillary placode, the rudiment of each circumvallate papilla and the developing circumvallate papilla itself from E13 to E19. However, postnatally, both α-gustducin and NCAM became concentrated within taste cells as the formation of taste buds advanced. After P14, neither NCAM nor α-gustducin was detectable in the epithelium around the taste buds. In conclusion, α-gustducin appeared in the cytoplasm of taste cells during their formation after birth, while NCAM appeared in the epithelium of the circumvallate papilla-forming area. However, these two markers of taste cells were similarly distributed within mature taste cells.
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Golden GJ, Ishiwatari Y, Theodorides ML, Bachmanov AA. Effect of chorda tympani nerve transection on salt taste perception in mice. Chem Senses 2011; 36:811-9. [PMID: 21743094 PMCID: PMC3195788 DOI: 10.1093/chemse/bjr056] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Effects of gustatory nerve transection on salt taste have been studied extensively in rats and hamsters but have not been well explored in the mouse. We examined the effects of chorda tympani (CT) nerve transection on NaCl taste preferences and thresholds in outbred CD-1 mice using a high-throughput phenotyping method developed in our laboratory. To measure taste thresholds, mice were conditioned by oral self-administration of LiCl or NaCl and then presented with NaCl concentration series in 2-bottle preference tests. LiCl-conditioned and control NaCl-exposed mice were given bilateral transections of the CT nerve (LiCl-CTX, NaCl-CTX) or were left intact as controls (LiCl-CNT, NaCl-CNT). After recovery from surgery, mice received a concentration series of NaCl (0–300 mM) in 48-h 2-bottle tests. CT transection increased NaCl taste thresholds in LiCl-conditioned mice and eliminated avoidance of concentrated NaCl in control NaCl-exposed mice. This demonstrates that in mice, the CT nerve is important for detection and recognition of NaCl taste and is necessary for the normal avoidance of high concentrations of NaCl. The results of this experiment also show that the method of high-throughput phenotyping of salt taste thresholds is suitable for detecting changes in the taste periphery in mouse genetic studies.
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Affiliation(s)
- Glen J Golden
- Monell Chemical Senses Center, Philadelphia, PA 19104-3308, USA.
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Pinto R, Frias B, Allen S, Dawbarn D, McMahon SB, Cruz F, Cruz CD. Sequestration of brain derived nerve factor by intravenous delivery of TrkB-Ig2 reduces bladder overactivity and noxious input in animals with chronic cystitis. Neuroscience 2010; 166:907-16. [PMID: 20079809 DOI: 10.1016/j.neuroscience.2010.01.015] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2009] [Revised: 11/18/2009] [Accepted: 01/08/2010] [Indexed: 01/20/2023]
Abstract
Brain derived nerve factor (BDNF) is a trophic factor belonging to the neurotrophin family. It is upregulated in various inflammatory conditions, where it may contribute to altered pain states. In cystitis, little is known about the relevance of BDNF in bladder-generated noxious input and bladder overactivity, a matter we investigated in the present study. Female rats were intraperitoneally (i.p.) injected with cyclophosphamide (CYP; 200 mg/kg). They received saline or TrkB-Ig(2) via intravenously (i.v.) or intravesical administration. Three days after CYP-injection, animals were anaesthetized and cystometries performed. All animals were perfusion-fixed and the spinal cord segments L6 collected, post-fixed and processed for c-Fos and phosphoERK immunoreactivity. BDNF expression in the bladder, as well as bladder histology, was also assessed. Intravesical TrkB-Ig(2) did not change bladder reflex activity of CYP-injected rats. In CYP-animals treated with i.v. TrkB-Ig(2) a decrease in the frequency of bladder reflex contractions, in comparison with saline-treated animals, was observed. In spinal sections from the latter group of animals, the number of phosphoERK and c-Fos immunoreactive neurons was lower than in sections from saline-treated CYP-animals. BDNF immunoreactivity was higher during cystitis but was not changed by TrkB-Ig(2) i.v. treatment. Evaluation of the bladder histology showed similar inflammatory signs in the bladders of inflamed animals, irrespective of the treatment. Data show that i.v. but not intravesical administration of TrkB-Ig(2) reduced bladder hyperactivity in animals with cystitis to levels comparable to those observed in unirritated rats. Since i.v. TrkB-Ig(2) also reduced spinal extracellular signal-regulated kinase (ERK) activation, it is possible that BDNF contribution to inflammation-induced bladder hyperactivity is via spinal activation of the ERK pathway. Finally, the reduction in c-Fos expression indicates that TrkB-Ig(2) also reduced bladder-generated noxious input. Our results show that sequestration of BDNF may be considered a new therapeutic strategy to treat chronic cystitis.
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Affiliation(s)
- R Pinto
- Instituto de Biologia Celular e Molecular, Porto, Portugal; Department of Urology, Hospital de S João, Porto, Portugal
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Expression of Sox2 in mouse taste buds and its relation to innervation. Cell Tissue Res 2008; 332:393-401. [PMID: 18379823 DOI: 10.1007/s00441-008-0600-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2007] [Accepted: 02/11/2008] [Indexed: 10/22/2022]
Abstract
Sox2, which encodes an HMG box transcription factor, is known to regulate the differentiation of progenitor cells of the tongue into taste bud cells versus keratinocytes during development. To determine the neural dependence of Sox2 expression, glossopharyngeal nerves of mice were cut bilaterally. In unoperated mice, the expression of Sox2 mRNA and protein was restricted to a subset of taste bud cells and to the epithelium surrounding the taste buds of the circumvallate papillae. During the period of denervation, the taste buds largely disappeared; the taste bud cells and the epithelial cells with Sox2-immunoreactive (IR) nuclei decreased in number and totally disappeared from the epithelium by 16 days after denervation. When regenerated nerve fibers entered the epithelium, Sox2 expression reappeared, first in the epithelial cells, and then in the regenerating taste bud cells. In prenatal mice, Sox2 was expressed in the epithelium of the dorsal surface of circumvallate papillae, in regions into which numerous nerve fibers had entered. The results suggested that Sox2 expression was dependent on gustatory innervation. Sox2-IR cells in the taste buds were also examined by double-immunolabeling for 5-bromo-2'-deoxyuridine and cell-type markers such as cytokeratin 14, neural cell adhesion molecule, inositol 1,4,5-triphosphate receptor 3, and blood group H antigen. Sox2-IR cells were found in the populations of basal cells and of immature and some mature taste bud cells. A large number of Sox2-IR cells were identified as type-I cells, with a few being type-II and type-III cells.
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20
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Suzuki Y, Mizoguchi I, Uchida N. Detection of neurotrophic factors in taste buds by laser capture microdissection, immunohistochemistry, and in situ hybridization. ACTA ACUST UNITED AC 2007; 70:117-26. [PMID: 17827669 DOI: 10.1679/aohc.70.117] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Neurotrophic factors are thought to function in the survival and maintenance of the taste buds and nerve fibers innervating them. Laser capture microdissection (LCM) coupled with the reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the mRNA of neurotrophic factors and their receptors in the taste buds of adult mouse circumvallate papillae. Results showed mRNAs of the ciliary neurotrophic factor (CNTF), its receptor (CNTFR), glial cell line-derived neurotrophic factor (GDNF), GDNF family receptors alpha-1 (GFRalpha-1), GFRalpha-2, and RET tyrosine kinase receptor (RET), neurotrophin (NT)3, NT4/5, tyrosine kinase (Trk) C, nerve growth factor (NGF), and TrkA were expressed in the isolated taste buds. Among these neurotrophic factors, GDNF, GFRalpha-1, GFRalpha-2, NT3, NT4/5, NGF, and TrkA were previously found in the taste buds immunohistochemically and were detected at the mRNA level in the present study. The present immunohistochemical study revealed that CNTF, CNTFR, and the RET tyrosine kinase receptor, which binds GDNF family/ receptor complexes, were also expressed in the taste buds. However, by in situ hybridization, mRNAs of CNTF and RET were not detected in the taste buds from adult mice although they were found in those from early postnatal mice. CNTFR mRNA did not show any specific pattern in the taste buds. Moreover, mRNA expressions of NT4/5 and TrkC was re-examined by in situ hybridization; however no specific pattern was found for them in the taste buds. In summary, LCM is a useful tool for the detection of a relatively small amount of mRNA, such as that of neurotrophic factors and receptors in the taste buds.
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Affiliation(s)
- Yuko Suzuki
- Division of Histology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
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21
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Guagliardo NA, Hill DL. Fungiform taste bud degeneration in C57BL/6J mice following chorda-lingual nerve transection. J Comp Neurol 2007; 504:206-16. [PMID: 17626272 PMCID: PMC2811721 DOI: 10.1002/cne.21436] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Taste buds are dependent on innervation for normal morphology and function. Fungiform taste bud degeneration after chorda tympani nerve injury has been well documented in rats, hamsters, and gerbils. The current study examines fungiform taste bud distribution and structure in adult C57BL/6J mice from both intact taste systems and after unilateral chorda-lingual nerve transection. Fungiform taste buds were visualized and measured with the aid of cytokeratin 8. In control mice, taste buds were smaller and more abundant on the anterior tip (<1 mm) of the tongue. By 5 days after nerve transection taste buds were smaller and fewer on the side of the tongue ipsilateral to the transection and continued to decrease in both size and number until 15 days posttransection. Degenerating fungiform taste buds were smaller due to a loss of taste bud cells rather than changes in taste bud morphology. While almost all taste buds disappeared in more posterior fungiform papillae by 15 days posttransection, the anterior tip of the tongue retained nearly half of its taste buds compared to intact mice. Surviving taste buds could not be explained by an apparent innervation from the remaining intact nerves. Contralateral effects of nerve transection were also observed; taste buds were larger due to an increase in the number of taste bud cells. These data are the first to characterize adult mouse fungiform taste buds and subsequent degeneration after unilateral nerve transection. They provide the basis for more mechanistic studies in which genetically engineered mice can be used.
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Affiliation(s)
- Nick A Guagliardo
- Department of Psychology, University of Virginia, Charlottesville, Virginia 22904-4400, USA
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22
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Abstract
The neurotrophin family of neurotrophic factors are well-known for their effects on neuronal survival and growth. Over the past decade, considerable evidence has accumulated from both humans and animals that one neurotrophin, nerve growth factor (NGF), is a peripheral pain mediator, particularly in inflammatory pain states. NGF is upregulated in a wide variety of inflammatory conditions, and NGF-neutralizing molecules are effective analgesic agents in many models of persistent pain. Such molecules are now being evaluated in clinical trials. NGF regulates the expression of a second neurotrophin, brain-derived neurotrophic factor (BDNF), in nociceptors. BDNF is released when nociceptors are activated, and it acts as a central modulator of pain. The chapter reviews the evidence for these roles (and briefly the effects of other neurotrophins), the range of conditions under which they act, and their mechanism of action.
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Affiliation(s)
- Sophie Pezet
- The London Pain Consortium, King's College London, The Wolfson Center for Age-Related Diseases, SE1 1UL London, United Kingdom.
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Ganchrow D, Ganchrow J, Witt M, Arki-Burstyn E. The effect of β-bungarotoxin, or geniculate ganglion lesion on taste bud development in the chick embryo. Histochem Cell Biol 2006; 126:419-35. [PMID: 16604348 DOI: 10.1007/s00418-006-0177-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2006] [Indexed: 11/29/2022]
Abstract
Chick taste bud (gemmal) primordia normally appear on embryonic day (E) 16 and incipient immature, spherical-shaped buds at E17. In ovo injection of beta-bungarotoxin at E12 resulted in a complete absence of taste buds in lower beak and palatal epithelium at developmental ages E17 and E21. However, putative gemmal primordia (solitary clear cells; small, cell groupings) remained, lying adjacent to salivary gland duct openings as seen in normal chick gemmal development. Oral epithelium was immunonegative to neural cell adhesion molecule (NCAM) suggesting gemmal primordia are nerve-independent. Some NCAM immunoreactivity was evident in autonomic ganglion-like cells and nerve fibers in connective tissue. After unilateral geniculate ganglion/otocyst excision on E2.5, at developmental ages E18 and posthatching day 1, approximately 12% of surviving ipsilateral geniculate ganglion cells sustained approximately 54% of the unoperated gemmal counts. After E18, proportional stages of differentiation in surviving developing buds probably reflect their degree of innervation, as well as rate of differentiation. Irrespective of the degree of geniculate ganglion damage, the proportion of surviving buds can be sustained at the same differentiated bud stage as on the unoperated side, or may differentiate to a later bud stage, consistent with the thesis that bud maturation, maintenance, and survival are nerve-dependent.
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Affiliation(s)
- Donald Ganchrow
- Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, 69978, Ramat Aviv, Tel-Aviv, Israel.
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Takeda M, Suzuki Y, Obara N, Tsunekawa H. Immunohistochemical detection of neurotrophin-3 and -4, and their receptors in mouse taste bud cells. ACTA ACUST UNITED AC 2006; 68:393-403. [PMID: 16505585 DOI: 10.1679/aohc.68.393] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Neurotrophin-3 (NT3) and neurotrophin-4 (NT4) affect the survival and maintenance of central and peripheral neurons. Using an immunohistochemical method, we examined whether the taste bud cells in the circumvallate papillae of normal mice expressed NT3, NT4, and their respective receptors TrkC and TrkB, and if so, what type of cells in the taste buds expressed them. Double immunostaining for either of them and PGP 9.5, NCAM, or gustducin was used to determine which cell types expressed which neurotrophins and receptors. Normal taste bud cells expressed NT3, NT4, and the TrkB receptor, but not TrkC. The percentage of NT3-immunoreactive cells among all taste bud cells was 89.0%, that of NT4-immunoreactive cells, 58.6%, and that of TrkB-immunoreactive cells, 80.8%. Almost none of the NT4-immunoreactive cells were reactive with anti-PGP 9.5 or the anti-NCAM antibody, but they could be stained with anti-gustducin, revealing that NT4-immunoreactive cells were contained only in the type-II--and possibly type-I--cell population. On the other hand, NT3-, and TrkB-immunoreactive cells included type-III cells, together with type-II, -I, and basal cells, because they were positive for PGP 9.5 and gustducin. We conclude that NT4 may exert trophic actions on all types of taste bud cells by binding to their TrkB receptors, and NT3 may also have a similar, though negligible role.
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Affiliation(s)
- Masako Takeda
- Department of Oral Anatomy, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido 061-0293, Japan.
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Lee MJ, Kim JY, Lee SI, Sasaki H, Lunny DP, Lane EB, Jung HS. Association of Shh and Ptc with keratin localization in the initiation of the formation of circumvallate papilla and von Ebner's gland. Cell Tissue Res 2006; 325:253-61. [PMID: 16552524 DOI: 10.1007/s00441-006-0160-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2005] [Accepted: 01/04/2006] [Indexed: 12/28/2022]
Abstract
The development of gustatory papillae in mammalian embryos requires the coordination of a series of morphological events, such as proliferation, differentiation and innervation. In mice, the circumvallate papilla (CVP) is a specialized structure that develops in a characteristic spatial and temporal pattern in the posterior region of the tongue dorsal surface. The distinct expression patterns of Shh and Ptc, which play important roles in the development of other epithelial appendages, have been localized in the trench wall that gives rise to von Ebner's gland (VEG). To define the cellular mechanisms responsible for morphogenesis and differentiation during early development of CVP and VEG, the localization patterns of keratins (cytokeratins) K7, K8, K18, K19, K14 and connexin-43, which are dependent on Shh expression in other developmental systems, have been examined in detail. The distinct localization of keratins K7, K8, K18, K19, K14 and connexin-43 in the epithelium giving rise to the CVP and VEG suggests that cytodifferentiation is established prior to morphological changes. Interestingly, the localization of proliferating cell nuclear antigen, a marker for cell proliferation, is similar to that of Shh. An understanding of the regulatory roles of cell-cell interactions and signalling molecules in orchestrating a mutual network will bring us nearer to defining the molecular and cellular mechanisms underlying morphogenesis in mammalian taste bud development.
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Affiliation(s)
- Min-Jung Lee
- Division in Anatomy, Developmental Biology, Research Center for Orofacial Hard Tissue Regeneration, Oral Science Research Center, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, Seoul, South Korea
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Ozdener H, Yee KK, Cao J, Brand JG, Teeter JH, Rawson NE. Characterization and long-term maintenance of rat taste cells in culture. Chem Senses 2006; 31:279-90. [PMID: 16452455 DOI: 10.1093/chemse/bjj030] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Taste cells have a limited life span and are replaced from a basal cell population, although the specific factors involved in this process are not well known. Short- and long-term cultures of other sensory cells have facilitated efforts to understand the signals involved in proliferation, differentiation, and senescence, yet few studies have reported successful primary culture protocols for taste cells. Furthermore, no studies have demonstrated both proliferation and differentiation in vitro. In this study, we have developed an in vitro culture system to maintain and utilize rat primary taste cells for more than 2 months without losing key molecular and biochemical features. Gustducin, phospholipase C-beta2 (PLC-beta2), T1R3, and T2R5 mRNA were detected in the cultured cells by reverse transcriptase-polymerase chain reaction. Western blot analysis demonstrated gustducin and PLC-beta2 expression in the same samples, which was confirmed by immunocytochemistry. Labeling with bromo-2-deoxyuridine (BrdU) demonstrated proliferation, and a subset of BrdU-labeled cells were also immunoreactive for either gustducin or PLC-beta2, indicating differentiation of newly generated cells in vitro. Cultured cells also exhibited increases in intracellular calcium in response to several taste stimuli. These results indicate that taste cells from adult rats can be generated and maintained under the described conditions for at least 2 months. This system will enable further studies of the processes involved in proliferation, differentiation, and function of mammalian taste receptor cells in an in vitro preparation.
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Affiliation(s)
- Hakan Ozdener
- Monell Chemical Senses Center, Philadelphia, PA 19104-3308, USA.
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Yee C, Bartel DL, Finger TE. Effects of glossopharyngeal nerve section on the expression of neurotrophins and their receptors in lingual taste buds of adult mice. J Comp Neurol 2005; 490:371-90. [PMID: 16127713 DOI: 10.1002/cne.20670] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The expression of neurotrophins and neurotrophin receptors is essential for the proper establishment and function of many sensory systems. To determine which neurotrophins and neurotrophin receptors are expressed in taste buds, and in taste buds of mice following denervation, antibodies directed against the neurotrophins and their receptors were applied to adult mouse gustatory tissue. Immunohistochemistry reveals that nerve growth factor (NGF)-like immunoreactive (LIR), tyrosine kinase (trk) A-LIR, trkB-LIR, and p75-LIR elongated, differentiated taste cells are present within all lingual taste buds, whereas neither neurotrophin (NT)-3- nor trkC-LIR was detected in taste cells. Double-label immunohistochemistry using markers of different taste cell types in brain-derived neurotrophic factor (BDNF)LacZ mice reveals that BDNF (beta-gal) and trkB colocalize, mainly in type III taste cells. NGF, pro-NGF, and trkA coexist in type II taste cells, i.e., those expressing phospholipase Cbeta2 (PLCbeta2). p75-LIR also is present in both BDNF and NGF taste cell populations. To determine the neural dependence of neurotrophin expression in adult taste buds, glossopharyngeal nerves were cut unilaterally. During the period of denervation (10 days to 3 weeks), taste buds largely disappear, and few neurotrophin-expressing cells are present. Three weeks after nerve transection, nerve fascicles on the operated side of the tongue exhibit BDNF-LIR, NGF-LIR, and ubiquitin carboxyl terminal hydrolase (PGP 9.5)-LIR. However, BDNF-LIR staining intensity but not NGF-LIR or PGP 9.5-LIR is increased in nerve fascicles on the operated compared with the unoperated side. Five weeks following nerve transection, NT and NT receptor expression resumes and appears normal in taste buds and nerves. These results indicate that neurotrophin expression in taste buds is dependent on gustatory innervation, but expression in nerves is not dependent on contact with taste buds.
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Affiliation(s)
- Cindy Yee
- Rocky Mountain Taste and Smell Center, Department of Cellular and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado 80045-6511, USA
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Oakley B, Witt M. Building sensory receptors on the tongue. ACTA ACUST UNITED AC 2005; 33:631-46. [PMID: 16217619 DOI: 10.1007/s11068-005-3332-0] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2005] [Accepted: 04/05/2005] [Indexed: 12/01/2022]
Abstract
Neurotrophins, neurotrophin receptors and sensory neurons are required for the development of lingual sense organs. For example, neurotrophin 3 sustains lingual somatosensory neurons. In the traditional view, sensory axons will terminate where neurotrophin expression is most pronounced. Yet, lingual somatosensory axons characteristically terminate in each filiform papilla and in each somatosensory prominence within a cluster of cells expressing the p75 neurotrophin receptor (p75NTR), rather than terminating among the adjacent cells that secrete neurotrophin 3. The p75NTR on special specialized clusters of epithelial cells may promote axonal arborization in vivo since its over-expression by fibroblasts enhances neurite outgrowth from overlying somatosensory neurons in vitro. Two classical observations have implicated gustatory neurons in the development and maintenance of mammalian taste buds--the early arrival times of embryonic innervation and the loss of taste buds after their denervation in adults. In the modern era more than a dozen experimental studies have used early denervation or neurotrophin gene mutations to evaluate mammalian gustatory organ development. Necessary for taste organ development, brain-derived neurotrophic factor sustains developing gustatory neurons. The cardinal conclusion is readily summarized: taste buds in the palate and tongue are induced by innervation. Taste buds are unstable: the death and birth of taste receptor cells relentlessly remodels synaptic connections. As receptor cells turn over, the sensory code for taste quality is probably stabilized by selective synapse formation between each type of gustatory axon and its matching taste receptor cell. We anticipate important new discoveries of molecular interactions among the epithelium, the underlying mesenchyme and gustatory innervation that build the gustatory papillae, their specialized epithelial cells, and the resulting taste buds.
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Affiliation(s)
- Bruce Oakley
- Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
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Nosrat IV, Agerman K, Marinescu A, Ernfors P, Nosrat CA. Lingual deficits in neurotrophin double knockout mice. ACTA ACUST UNITED AC 2005; 33:607-15. [PMID: 16217617 DOI: 10.1007/s11068-005-3330-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2004] [Revised: 01/25/2005] [Accepted: 06/05/2005] [Indexed: 11/27/2022]
Abstract
Brain-derived neurotrophic factor (BDNF) and Neurotrophin 3 (NT-3) are members of the neurotrophin family and are expressed in the developing and adult tongue papillae. BDNF null-mutated mice exhibit specific impairments related to innervation and development of the gustatory system while NT-3 null mice have deficits in their lingual somatosensory innervation. To further evaluate the functional specificity of these neurotrophins in the peripheral gustatory system, we generated double BDNF/NT-3 knockout mice and compared the phenotype to BDNF(-/-) and wild-type mice. Taste papillae morphology was severely distorted in BDNF(-/-) xNT-3(-/-) mice compared to single BDNF(-/-) and wild-type mice. The deficits were found throughout the tongue and all gustatory papillae. There was a significant loss of fungiform papillae and the papillae were smaller in size compared to BDNF(-/-) and wild-type mice. Circumvallate papillae in the double knockouts were smaller and did not contain any intraepithelial nerve fibers. BDNF(-/-) xNT-3(-/-) mice exhibited additive losses in both somatosensory and gustatory innervation indicating that BDNF and NT-3 exert specific roles in the innervation of the tongue. However, the additional loss of fungiform papillae and taste buds in BDNF(-/-) xNT-3(-/-) mice compared to single BDNF knockout mice indicate a synergistic functional role for both BDNF-dependent gustatory and NT-3-dependent somatosensory innervations in taste bud and taste papillae innervation and development.
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Affiliation(s)
- Irina V Nosrat
- Laboratory of Oral Neurobiology, Department of Biological and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA
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Takeda M, Suzuki Y, Obara N, Uchida N, Kawakoshi K. Expression of glial cell line-derived neurotrophic factor (GDNF) and GDNF family receptor alpha1 in mouse taste bud cells after denervation. Anat Sci Int 2005; 80:105-10. [PMID: 15960316 DOI: 10.1111/j.1447-073x.2005.00105.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Glial cell line-derived neurotrophic' factor (GDNF) has been isolated as a neurotrophic factor that affects the survival and maintenance of central and peripheral neurons. Using immunocytochemical methods, we examined whether the taste bud cells in mouse circumvallate papillae after transection of the glossopharyngeal nerves expressed GDNF and its receptor, GDNF family receptor alpha1 (GFRalpha1). By 5 and 10 days after denervation, the number of taste buds had decreased markedly; however, the remaining taste bud cells still expressed GDNF and GFRalpha1. By 14 days after denervation, most of the taste buds had disappeared and GDNF- and GFRalpha1-immunoreactive cells were not seen. By 4 weeks after denervation, numerous TrkB-immunoreactive nerve fibers had invaded the papilla and a few taste buds expressing GDNF and GFRalpha1 had regenerated. Thus, GDNF- and GFRalpha1-immunoreactive taste bud cells after denervation vanished following the disappearance of the taste buds and reappeared at the same time as the taste buds reappeared.
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Affiliation(s)
- Masako Takeda
- Department of Oral Anatomy, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, Japan.
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Kawakoshi K, Suzuki Y, Okumura K, Shibata T, Takeda M. Expression of Nerve Growth Factor and Neurturin, and Their Receptors in Mouse Taste Buds. J Oral Biosci 2005. [DOI: 10.1016/s1349-0079(05)80023-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Takeda M, Suzuki Y, Obara N, Uchida N, Kawakoshi K. Expression of GDNF and GFR?1 in mouse taste bud cells. J Comp Neurol 2004; 479:94-102. [PMID: 15389609 DOI: 10.1002/cne.20315] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
GDNF (glial cell line-derived neurotrophic factor) affects the survival and maintenance of central and peripheral neurons. Using an immunocytochemical method, we examined whether the taste bud cells in the circumvallate papillae of normal mice expressed GDNF and its GFR alpha 1 receptor. Using double immunostaining for either of them and NCAM, PGP 9.5, or alpha-gustducin, we additionally sought to determine what type of taste bud cells expressed GDNF or GFR alpha 1, because NCAM is reported to be expressed in type-III cells, PGP 9.5, in type-III and some type-II cells, and alpha-gustducin, in some type-II cells. Normal taste bud cells expressed both GDNF and GFR alpha 1. The percentage of GDNF-immunoreactive cells among all taste bud cells was 31.63%, and that of GFR alpha 1-immunoreactive cells, 83.21%. Confocal laser scanning microscopic observations after double immunostaining showed that almost none of the GDNF-immunoreactive cells in the taste buds were reactive with anti-NCAM or anti-PGP 9.5 antibody, but could be stained with anti-alpha-gustducin antibody. On the other hand, almost all anti-PGP 9.5- or anti-alpha-gustducin-immunoreactive cells were positive for GFR alpha 1. Thus, GDNF-immunoreactive cells did not include type-III cells, but type-II cells, which are alpha-gustducin-immunoreactive; on the other hand, GFR alpha 1-immunoreactive cells included type-II and -III cells, and perhaps type-I cells. We conclude that GDNF in the type-II cells may exert trophic actions on type-I, -II, and -III taste bud cells by binding to their GFR alpha 1 receptors.
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Affiliation(s)
- Masako Takeda
- Department of Oral Anatomy, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido 061-0293, Japan.
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