Development of therapeutic strategy for neurodevelopmental disorders based on site-specific microglial and microRNA functions

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460345
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Nippon Medical School
• Principal Investigator: Suzuki Hidenori 日本医科大学, 医学(系)研究科(研究院), 教授 (30221328)
• Co-Investigator(Kenkyū-buntansha): SAITOW FUMIHITO 日本医科大学, 医学部, 准教授 (20360175) ; SAKAI ATSUSHI 日本医科大学, 医学部, 講師 (30386156) ; NAGANO MASATOSHI 日本医科大学, 医学部, 講師 (60271350)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 自閉症動物モデル / 社会的行動 / 背側縫線核 / 発達障害 / 不安様行動 / 扁桃体 / microRNA / ミクログリア

Outline of Final Research Achievements

The underlying neural mechanisms of neurodevelopmental disorders including autism spectrum disorder (ASD) are poorly understood. We examined an involvement of microglia in ASD using mice with paternal duplication (patDp/+) corresponding to human chromosome 15q11-q13. Iba1, a microglial activation marker, was decreased in the basolateral amygdala in patDp/+ mice at postnatal day 7. Perinatal treatment with minocycline, a microglial modulator, restored the Iba1 expression in the basolateral amygdala and reduced anxiety-related behaviors in adolescence. Further, early postnatal treatment with a selective serotonin reuptake inhibitor, which has been reported to directly affect microglial functions, ameliorated a deficit in social interaction behavior in adolescence.
The results of the present study suggest important roles of microglia in pathophysiology of neurodevelopmental disorders and provide a key piece of information to develop novel microglia-related drugs for these disorders.

Free Research Field

神経薬理学