An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism

作者：Meziane Hamid; Schaller Fabienne; Bauer Sylvian; Villard Claude; Matarazzo Valery; Riet Fabrice; Guillon Gilles; Lafitte Daniel; Desarmenien Michel G; Tauber Maithe; Muscatelli Francoise^*

来源：Biological Psychiatry, 2015, 78(2): 85-94.

DOI：10.1016/j.biopsych.2014.11.010

• Autism spectrum disorder
• MAGEL2
• Neurodevelopment
• Oxytocin
• Prader-Willi syndrome
• Therapy

BACKGROUND: Mutations of MAGEL2 have been reported in patients presenting with autism, and loss of MAGEL2 is also associated with Prader-Willi syndrome, a neurodevelopmental genetic disorder. This study aimed to determine the behavioral phenotype of Magel2-deficient adult mice, to characterize the central oxytocin (OT) system of these mutant mice, and to test the curative effect of a peripheral OT treatment just after birth.
METHODS: We assessed the social and cognitive behavior of Magel2-deficient mice, analyzed the OT system of mutant mice treated or not by a postnatal administration of OT, and determined the effect of this treatment on the brain.
RESULTS: Magel2 inactivation induces a deficit in social recognition and social interaction and a reduced learning ability in adult male mice. In these mice, we reveal anatomical and functional modifications of the OT system and show that these defects change from birth to adulthood. Daily administration of OT in the first postnatal week was sufficient to prevent deficits in social behavior and learning abilities in adult mutant male mice. We show that this OT treatment partly restores a normal OT system. Thus, we report that an alteration of the OT system around birth has long-term consequences on behavior and on cognition. Importantly, an acute OT treatment of Magel2-deficient pups has a curative effect.
CONCLUSIONS: Our study reveals that OT plays a crucial role in setting social behaviors during a period just after birth. An early OT treatment in this critical period could be a novel therapeutic approach for the treatment of neurodevelopmental disorders such as Prader-Willi syndrome and autism.

• 出版日期2015-7-15