Control of Social Withdrawal of Mice Deficient for the Autism Gene Magel2 by Restoration of Vasopressin-Oxytocin Dialogue in Septum
2019
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
vasopressinand
oxytocinin the lateral septum, a
region organizingsequential 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 actionsof
vasopressinand
oxytocinin the lateral septum as a key factor in the pathophysiology.
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