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
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
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DOI：
10.1016/j.biopsych.2014.11.010
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发表时间：
2015-07-15
影响因子：
10.6
通讯作者：
Muscatelli, Francoise
中科院分区：
文献类型：
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作者：
Meziane, Hamid;Schaller, Fabienne;Muscatelli, Francoise
背景：据报道，自闭症患者存在 MAGEL2 突变，MAGEL2 缺失也与普瑞德-威利综合征（一种神经发育遗传性疾病）相关。本研究旨在确定Magel2缺陷成年小鼠的行为表型，表征这些突变小鼠的中枢催产素（OT）系统，并测试出生后外周催产素（OT）治疗的疗效。方法：我们评估了Magel2缺陷小鼠的社会和认知行为，分析了出生后接受或未接受OT治疗的突变小鼠的OT系统，并确定了这种治疗对大脑的影响。失活会导致成年雄性小鼠的社会识别和社会互动缺陷以及学习能力下降。在这些小鼠中，我们揭示了 OT 系统的解剖学和功能性改变，并表明这些缺陷从出生到成年都会发生变化。在出生后第一周每天进行 OT 足以预防成年突变雄性小鼠的社交行为和学习能力缺陷。我们证明这种 OT 治疗可以部分恢复正常的 OT 系统。因此，我们报告说，出生前后 OT 系统的改变会对行为和认知产生长期影响。重要的是，对 Magel2 缺陷幼犬进行急性 OT 治疗具有疗效。结论：我们的研究表明，OT 在出生后一段时间内的社会行为设定中发挥着至关重要的作用。在这个关键时期进行早期 OT 治疗可能是治疗普拉德威利综合征和自闭症等神经发育障碍的一种新方法。
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.