Inhibition of Trpv4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
26
01
2021
accepted:
23
12
2021
revised:
08
12
2021
pubmed:
14
1
2022
medline:
26
5
2022
entrez:
13
1
2022
Statut:
ppublish
Résumé
Mutations in the SHANK3 gene have been recognized as a genetic risk factor for Autism Spectrum Disorder (ASD), a neurodevelopmental disease characterized by social deficits and repetitive behaviors. While heterozygous SHANK3 mutations are usually the types of mutations associated with idiopathic autism in patients, heterozygous deletion of Shank3 gene in mice does not commonly induce ASD-related behavioral deficit. Here, we used in-vivo and ex-vivo approaches to demonstrate that region-specific neonatal downregulation of Shank3 in the Nucleus Accumbens promotes D1R-medium spiny neurons (D1R-MSNs) hyperexcitability and upregulates Transient Receptor Potential Vanilloid 4 (Trpv4) to impair social behavior. Interestingly, genetically vulnerable Shank3
Identifiants
pubmed: 35022531
doi: 10.1038/s41380-021-01427-0
pii: 10.1038/s41380-021-01427-0
pmc: PMC9126815
doi:
Substances chimiques
Microfilament Proteins
0
Nerve Tissue Proteins
0
SHANK3 protein, human
0
Shank3 protein, mouse
0
TRPV Cation Channels
0
TRPV4 protein, human
0
Trpv4 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2080-2094Informations de copyright
© 2022. The Author(s).
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