title: 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.
abstract: 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.
authors.affiliation: Institut de la Clinique de la Souris, Strasbourg.
authors.forename: Hamid
authors.initials: H
authors.lastname: Meziane
authors.affiliation: Institut de Neurobiologie de la Méditerranée; Aix-Marseille Université, Marseille.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Schaller
authors.affiliation: Institut de Neurobiologie de la Méditerranée; Aix-Marseille Université, Marseille.
authors.forename: Sylvian
authors.initials: S
authors.lastname: Bauer
authors.affiliation: Plateforme Protéomique et Innovation Technologique Timone, Marseille.
authors.forename: Claude
authors.initials: C
authors.lastname: Villard
authors.affiliation: Institut de Neurobiologie de la Méditerranée; Aix-Marseille Université, Marseille.
authors.forename: Valery
authors.initials: V
authors.lastname: Matarazzo
authors.affiliation: Institut de la Clinique de la Souris, Strasbourg.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Riet
authors.affiliation: Institut de Génomique Fonctionnelle, National Centre for Scientific Research, Universités de Montpellier 1 and 2, Montpellier.
authors.forename: Gilles
authors.initials: G
authors.lastname: Guillon
authors.affiliation: Plateforme Protéomique et Innovation Technologique Timone, Marseille.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lafitte
authors.affiliation: Institut de Génomique Fonctionnelle, National Centre for Scientific Research, Universités de Montpellier 1 and 2, Montpellier.
authors.forename: Michel G
authors.initials: MG
authors.lastname: Desarmenien
authors.affiliation: Unité d'endocrinologie et Centre de Référence du Syndrome de Prader-Willi (MT), Centre de Physiopathologie de Toulouse-Purpan, Hôpital des enfants, Toulouse, France.
authors.forename: Maithé
authors.initials: M
authors.lastname: Tauber
authors.affiliation: Institut de Neurobiologie de la Méditerranée; Aix-Marseille Université, Marseille. Electronic address: francoise.muscatelli@inserm.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Muscatelli
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D001321:Autistic Disorder / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D001921:Brain / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010121:Oxytocin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D011218:Prader-Willi Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D011506:Proteins / Q000235:genetics*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012919:Social Behavior; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
chemical_list: D000951:Antigens, Neoplasm; D010121:Oxytocin; D011506:Proteins; C403091:Magel2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
keywords: Autism spectrum disorder; MAGEL2; Neurodevelopment; Oxytocin; Prader-Willi syndrome; Therapy