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Séminaire - Françoise MuscatelliOxytocin gives the tempo of feeding and social behaviors: a Prader-Willi syndrome mouse model.

Abstract :

Prader-Willi syndrome is one of the best-studied neurodevelopmental genetic disease characterized mainly as a feeding disorder with behavioral and social disturbances. PWS involves several contiguous genes, including the MAGEL2 gene. Recently, pathogenic mutations of MAGEL2 have also been reported in several patients causing autism and PWS- like phenotypes; all patients presented autistic symptoms and feeding difficulties in infancy. We generated Magel2-deficient (KO) mice that showed a decrease in mature oxytocin (OT) production, which was correlated with alterations of the onset of feeding behavior at birth and with alterations of social behavior and cognition in adult.
Moreover, of great relevance, is the finding that a postnatal administration of OT restores a normal suckling activity and cures PWS symptoms of Magel2-deficient mice in adulthood. Our working hypothesis is that the lack of Magel2 expression leads to an early postnatal alteration in OT neurons, affecting release of OT in structures controlling food intake/suckling and that this early deficit has later impairments of axonal wiring of OT neurons and inducing altered social behavior in adulthood.

Thus, this model is perfectly suited for understanding the early alterations of the OT-system in PWS/autism and the rescue effect of an early OT administration. Furthermore, our study revealed that OT is a key factor in the initiation of suckling activity.

Selected publications

1. Valery Grinevich, Michel G. Desarménien, Bice Chini Maithé Tauber and Françoise Muscatelli. Ontogenesis of oxytocin pathways in the mammalian brain: late maturation and psychosocial disorders. Front. Neuroanat., doi: 10.3389/fnana.2014.00164, 2015

2. H. Meziane, F.Schaller, S. Bauer, C. Villard, V. Matarazzo, F. Riet, G. Guillon, D. Lafitte, M. G. Desarmenien, M. Tauber and F. Muscatelli. 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. Biological Psychiatry, 78(2):85-94, 2015

3. Schaller, F., Watrin, F., Sturny, R., Massacrier, A., Szepetowski, P. and Muscatelli, F. A single postnatal injection of oxytocin rescues the lethal feeding behaviour in mice deficient for the Prader- Willi Magel2 gene. Hum. Mol. Genet. 2010. 19(24), 4895-905