| Title: |
The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice |
| Authors: |
Favier, Mathieu; Martín-García, Elena; Icick, Romain; de Almeida, Camille; Jehl, Joachim; Desplanque, Mazarine; Zimmermann, Johannes; Henrion, Annabelle; Mansouri-Guilani, Nina; Mounier, Coline; Ribeiro, Svethna; Henderson, Fiona; Geoffroy, Andrea; Mella, Sebastien; Poirel, Odile; Bernard, Véronique; Fabre, Véronique; Li, Yulong; Rosenmund, Christian; Jamain, Stéphane; Vorspan, Florence; Mourot, Alexandre; Duriez, Philibert; Pinhas, Leora; Maldonado, Rafael; Pietrancosta, Nicolas; Daumas, Stéphanie; El Mestikawy, Salah |
| Publication Year: |
2024 |
| Collection: |
Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB |
| Subject Terms: |
Transporters in the nervous system; Addiction; Feeding behaviour |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
38971801 |
| Relation: |
Nature communications; Vol. 15 (july 2024); https://ddd.uab.cat/record/306898; urn:oai:ddd.uab.cat:306898; urn:pmcid:PMC11227582; urn:pmid:38971801; urn:oai:pubmedcentral.nih.gov:11227582 |
| Availability: |
https://ddd.uab.cat/record/306898 |
| Rights: |
open access ; 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. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.FF893743 |
| Database: |
BASE |