Control of Social Withdrawal of Mice Deficient for the Autism Gene Magel2 by Restoration of Vasopressin-Oxytocin Dialogue in Septum

Amélie Borie (1) , Yann Dromard (1) , Djodi Dufner (1) , Emi Pollozi (1) , Damien Huzard (1) , Csaba Tomboli , Alexandra Olma (2) , Maurice Manning (2) , Pascal Colson (1) , Gilles Guillon (1) , Francoise Muscatelli (3) , Michel G Desarménien (1) , Freddy Jeanneteau (1)

1 IGF - Institut de Génomique Fonctionnelle
2 Department of Chemistry, University of Toledo
3 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]

Intellectual and social disabilities are common comorbidities in adolescents and adults with Magel2 gene deficiency characterizing the Prader-Willi and Schaaf-Yang neurodevelopmental syndromes. The cellular and molecular mechanisms underlying the risk for autism in these syndromes are unexplored. Here we used Magel2 knockout mice combined with optogenetic/pharmacological tools to characterize disease modifications in the social brain network. We find that the degree of social novelty moderates a dialogue between vasopressin and oxytocin in the lateral septum, a region organizing sequential content of sensory experiences. Social withdrawal of mice lacking Magel2 is alleviated by restoration of dialogue-lead by vasopressin. This preclinical study identifies the collective actions of vasopressin and oxytocin in the lateral septum as a key factor in the pathophysiology.

Domaines: Sciences du Vivant [q-bio]

Amélie Borie, Yann Dromard, Djodi Dufner, Emi Pollozi, Damien Huzard, et al.. Control of Social Withdrawal of Mice Deficient for the Autism Gene Magel2 by Restoration of Vasopressin-Oxytocin Dialogue in Septum. 2020. ⟨hal-02990176⟩