The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice
Favier, Mathieu (McGill University (Montreal, Canadà))
Martín-García, Elena 1975- (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de les Ciències de la Salut)
Icick, Romain (Université Paris Cité)
de Almeida, Camille (Sorbonne Université)
Jehl, Joachim (PSL Research University (Paris, França))
Desplanque, Mazarine (Sorbonne Université)
Zimmermann, Johannes (Charite Universitaetsmedizin (Belin, Alemanya))
Henrion, Annabelle (Université Paris Est Créteil)
Mansouri-Guilani, Nina (NSorbonne Université)
Mounier, Coline (McGill University (Montreal, Canadà))
Ribeiro, Svethna (McGill University (Montreal, Canadà))
Henderson, Fiona (Sorbonne Université)
Geoffroy, Andrea (Sorbonne Université)
Mella, Sebastien (Sorbonne Université)
Poirel, Odile (Sorbonne Université)
Bernard, Véronique (Sorbonne Université)
Fabre, Véronique (Sorbonne Université)
Li, Yulong (Peking University School of Life Sciences)
Rosenmund, Christian (Charite Universitaetsmedizin (Belin, Alemanya))
Jamain, Stéphane (Université Paris Est Créteil)
Vorspan, Florence (Université Paris Cité)
Mourot, Alexandre (PSL Research University (Paris, França))
Duriez, Philibert (Centre hospitalier Sainte-Anne (Paris, França))
Pinhas, Leora (PHLIP Mental Health and Painless Medicine clinic (Toronto, Canadà))
Maldonado, Rafael 1961- (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de les Ciències de la Salut)
Pietrancosta, Nicolas (Sorbonne Paris Cité)
Daumas, Stéphanie (Sorbonne Université)
El Mestikawy, Salah (Sorbonne Université)

Date:	2024
Abstract:	Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p. T8I, was identified in patients with substance use disorders (SUDs) and eating disorders (EDs). A mouse line was generated to understand the neurochemical and behavioral impact of the p. T8I variant. In VGLUT3 T8I/T8I male mice, glutamate signaling was unchanged but vesicular synergy and ACh release were blunted. Mutant male mice exhibited a reduced DA release in the dorsomedial striatum but not in the dorsolateral striatum, facilitating habit formation and exacerbating maladaptive use of drug or food. Increasing ACh tone with donepezil reversed the self-starvation phenotype observed in VGLUT3 T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs. The VGLUT3-p. T8I mutation was identified in patients with SUDs and EDs and introduced in a mouse line. Here, authors show that mutant mice have an imbalanced DA signaling in the dorsal striatum associated with maladaptive cocaine and food consumption.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Transporters in the nervous system ; Addiction ; Feeding behaviour
Published in:	Nature communications, Vol. 15 (july 2024) , ISSN 2041-1723

DOI: 10.1038/s41467-024-49371-1
PMID: 38971801

19 p, 2.1 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles