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

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http://hdl.handle.net/10138/327712

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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

Julkaisun nimi: Cerebral Dopamine Neurotrophic Factor Is Essential for Enteric Neuronal Development, Maintenance and Regulation of Gastrointestinal Transit
Tekijä: Chalazonitis, Alcmène; Li, ZhiShan; Pham, Tuan D.; Chen, Jason; Rao, Meenakshi; Lindholm, Päivi; Saarma, Mart; Lindahl, Maria; Gershon, Michael D.
Tekijän organisaatio: Institute of Biotechnology
Helsinki Institute of Life Science HiLIFE
University of Helsinki
Helsinki One Health (HOH)
Päiväys: 2020-10
Kieli: eng
Sivumäärä: 25
Kuuluu julkaisusarjaan: Journal of Comparative Neurology
ISSN: 0021-9967
DOI-tunniste: https://doi.org/10.1002/cne.24901
URI: http://hdl.handle.net/10138/327712
Tiivistelmä: 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.
Avainsanat: 3124 Neurology and psychiatry
Enteric nervous system
submucosal plexus
dopaminergic neurons
bone morphogenetic protein-4
serotonin
glial cell line derived neurotrophic factor
NERVOUS-SYSTEM
SEROTONIN TRANSPORTER
ALPHA-SYNUCLEIN
MICE LACKING
IN-VITRO
SUBMUCOSAL GANGLIA
FETAL-RAT GUT
enteric nervous system
CREST-DERIVED PRECURSORS
NEURAL CREST
PARKINSONS-DISEASE
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: unspecified
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: acceptedVersion


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