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
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
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 / セロトニン神経系 / 自閉症 / 発達障害モデル動物 / miRNA / オープンフィールド試験 / 中脳背側縫線核 |
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.
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