Venue : Centre Broca Nouvelle-Aquitaine 
Salah El Mestikawy
McGill University, Douglas Institute, Montreal, Canada
CNRS, Paris
https://douglas.research.mcgill.ca/fr/salah-el-mestikawy-2/
Invited by Etienne Herzog (IINS)
Title
A rare variant of VGLUT3 (p.T8I) involved in substance use disorders and eating disorders: Opening the door to a treatment of anorexia nervosa ?
Summary
Cholinergic interneurons (Chis) are pivotal regulators of striatal functions. They have the particularity to express both the vesicular acetylcholine transporter (VAChT) and the atypical type 3 vesicular glutamate transporter (VGLUT3). Consequently, they regulate the striatal network with both acetylcholine (ACh) and glutamate. We previously identified the missense polymorphism VGLUT3-p.T8I (threonine at position 8 changed to an isoleucine) in patients with substance use disorders (SUD) or eating disorders (ED). Using a rodent model (VGLUT3T8I/T8I mice), we found that the variant was causative in SUD and ED and identified an underlying mechanism. This led to a treatment that alleviate ED in mutant mice and potentially in humans.
Selected publications
El Mestikawy S, Wallen-Mackenzie A, Fortin GM, Descarries L, Trudeau LE. From glutamate co-release to vesicular synergy: vesicular glutamate transporters. Nat Rev Neurosci 12, 204-216 (2011).
Everitt BJ, Robbins TW. Drug Addiction: Updating Actions to Habits to Compulsions Ten Years On. Annu Rev Psychol 67, 23-50 (2016).
Favier M, et al. Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating. J Clin Invest 130, 6616-6630 (2020).
Godier LR, Park RJ. Compulsivity in anorexia nervosa: a transdiagnostic concept. Front Psychol 5, 778 (2014).
Sakae DY, et al. The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens. Mol Psychiatry 20, 1448-1459 (2015).
Steinglass JE, Walsh BT. Neurobiological model of the persistence of anorexia nervosa. J Eat Disord 4, 19 (2016).