Cerebral Dopamine Neurotrophic Factor Is Essential for Enteric Neuronal Development, Maintenance and Regulation of Gastrointestinal Transit

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dc.contributor.author Chalazonitis, Alcmène
dc.contributor.author Li, ZhiShan
dc.contributor.author Pham, Tuan D.
dc.contributor.author Chen, Jason
dc.contributor.author Rao, Meenakshi
dc.contributor.author Lindholm, Päivi
dc.contributor.author Saarma, Mart
dc.contributor.author Lindahl, Maria
dc.contributor.author Gershon, Michael D.
dc.date.accessioned 2021-03-09T23:03:27Z
dc.date.available 2021-12-18T03:46:06Z
dc.date.issued 2020-10
dc.identifier.citation Chalazonitis , A , Li , Z , Pham , T D , Chen , J , Rao , M , Lindholm , P , Saarma , M , Lindahl , M & Gershon , M D 2020 , ' Cerebral Dopamine Neurotrophic Factor Is Essential for Enteric Neuronal Development, Maintenance and Regulation of Gastrointestinal Transit ' , Journal of Comparative Neurology , vol. 528 , no. 14 , pp. 2420-2444 . https://doi.org/10.1002/cne.24901
dc.identifier.other PURE: 133712862
dc.identifier.other PURE UUID: 341f8d10-49bb-44eb-9544-65a8de00ad32
dc.identifier.other RIS: urn:522BC0345FDD4D3F3BA034B437EA1FFE
dc.identifier.other WOS: 000521617000001
dc.identifier.other ORCID: /0000-0002-5674-8830/work/79518220
dc.identifier.other ORCID: /0000-0001-5543-7160/work/79521738
dc.identifier.other ORCID: /0000-0003-3022-5035/work/85429896
dc.identifier.uri http://hdl.handle.net/10138/327712
dc.description.abstract Abstract Cerebral dopamine neurotrophic factor (CDNF) is expressed in the brain and is neuroprotective. We have previously shown that CDNF is also expressed in the bowel and that its absence leads to degeneration and autophagy in the enteric nervous system (ENS), particularly in the submucosal plexus. We now demonstrate that enteric CDNF immunoreactivity is restricted to neurons (submucosal > myenteric) and is not seen in glia, interstitial cells of Cajal, or smooth muscle. Expression of CDNF, moreover, is essential for the normal development and survival of enteric dopaminergic neurons; thus, expression of the dopaminergic neuronal markers, dopamine, tyrosine hydroxylase, and dopamine transporter are deficient in the ileum of Cdnf -/- mice. The normal age-related decline in proportions of submucosal dopaminergic neurons is exacerbated in Cdnf -/- animals. The defect in Cdnf -/- animals is not dopamine-restricted; proportions of other submucosal neurons (NOS-, GABA-, and CGRP-expressing), are also deficient. The deficits in submucosal neurons are reflected functionally in delayed gastric emptying, slowed colonic motility, and prolonged total gastrointestinal transit. CDNF is expressed selectively in isolated enteric neural crest-derived cells (ENCDC), which also express the dopamine-related transcription factor Foxa2. Addition of CDNF to ENCDC promotes development of dopaminergic neurons; moreover, survival or these neurons becomes CDNF-dependent after exposure to bone morphogenetic protein 4. The effects of neither glial cell-derived neurotrophic factor (GDNF) nor serotonin are additive with CDNF. We suggest that CDNF plays a critical role in development and long-term maintenance of dopaminergic and other sets of submucosal neurons. This article is protected by copyright. All rights reserved. en
dc.format.extent 25
dc.language.iso eng
dc.relation.ispartof Journal of Comparative Neurology
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3124 Neurology and psychiatry
dc.subject Enteric nervous system
dc.subject submucosal plexus
dc.subject dopaminergic neurons
dc.subject bone morphogenetic protein-4
dc.subject serotonin
dc.subject glial cell line derived neurotrophic factor
dc.subject MICE LACKING
dc.subject IN-VITRO
dc.subject FETAL-RAT GUT
dc.subject enteric nervous system
dc.subject NEURAL CREST
dc.title Cerebral Dopamine Neurotrophic Factor Is Essential for Enteric Neuronal Development, Maintenance and Regulation of Gastrointestinal Transit en
dc.type Article
dc.contributor.organization Institute of Biotechnology
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization University of Helsinki
dc.contributor.organization Helsinki One Health (HOH)
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1002/cne.24901
dc.relation.issn 0021-9967
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion

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