The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Favier, Mathieu
• dc.contributor.author Martín García, Elena, 1975-
• dc.contributor.author Maldonado, Rafael, 1961-
• dc.contributor.author El Mestikawy, Salah
• dc.date.accessioned 2024-09-17T06:24:34Z
• dc.date.available 2024-09-17T06:24:34Z
• dc.date.issued 2024
• dc.description.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 VGLUT3T8I/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 VGLUT3T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs.
• dc.format.mimetype application/pdf
• dc.identifier.citation Favier M, Martin Garcia E, Icick R, de Almeida C, Jehl J, Desplanque M, et al. The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice. Nat Commun. 2024 Jul 7;15(1):5691. DOI: 10.1038/s41467-024-49371-1
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-024-49371-1
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/61113
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2024 Jul 7;15(1):5691
• dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Addiction
• dc.subject.keyword Feeding behaviour
• dc.subject.keyword Transporters in the nervous system
• dc.title The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion