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

Borie, A. M.; Dromard, Y.; Dufner, D.; Pollozi, E.; Huzard, D.; Tomboli, C.; Olma, A.; Manning, M.; Colson, P.; Guillon, G.; Muscatelli, F.; Desarmenien, M. G.; Jeanneteau, F.

doi:10.1101/800425

bioRxiv · 10.1101/800425

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

Borie, A. M.·Dromard, Y.·Dufner, D.·Pollozi, E.·Huzard, D.·Tomboli, C.·Olma, A.·Manning, M.·Colson, P.·Guillon, G.·Muscatelli, F.·Desarmenien, M. G.·Jeanneteau, F.

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Abstract

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.

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Borie, A. M., Dromard, Y., Dufner, D., Pollozi, E., Huzard, D., Tomboli, C., Olma, A., Manning, M., Colson, P., Guillon, G., Muscatelli, F., Desarmenien, M. G., Jeanneteau, F.. 2019-10-10. Control of Social Withdrawal of Mice Deficient for the Autism Gene Magel2 by Restoration of Vasopressin-Oxytocin Dialogue in Septum. https://doi.org/10.1101/800425

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