Sex dimorphism controls dysbindin-related cognitive dysfunctions in mice and humans with the contribution of COMT.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
26 Mar 2024
26 Mar 2024
Historique:
received:
10
09
2023
accepted:
12
03
2024
revised:
05
03
2024
medline:
27
3
2024
pubmed:
27
3
2024
entrez:
27
3
2024
Statut:
aheadofprint
Résumé
Cognitive dysfunctions are core-enduring symptoms of schizophrenia, with important sex-related differences. Genetic variants of the DTBPN1 gene associated with reduced dysbindin-1 protein (Dys) expression negatively impact cognitive functions in schizophrenia through a functional epistatic interaction with Catechol-O-methyltransferase (COMT). Dys is involved in the trafficking of dopaminergic receptors, crucial for prefrontal cortex (PFC) signaling regulation. Moreover, dopamine signaling is modulated by estrogens via inhibition of COMT expression. We hypothesized a sex dimorphism in Dys-related cognitive functions dependent on COMT and estrogen levels. Our multidisciplinary approach combined behavioral-molecular findings on genetically modified mice, human postmortem Dys expression data, and in vivo fMRI during a working memory task performance. We found cognitive impairments in male mice related to genetic variants characterized by reduced Dys protein expression (p
Identifiants
pubmed: 38532008
doi: 10.1038/s41380-024-02527-3
pii: 10.1038/s41380-024-02527-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
ID : 201779W93T
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
ID : 2017K2NEF4
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
ID : 2017K2NEF4
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
ID : 2017K2NEF4
Informations de copyright
© 2024. The Author(s).
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