| Project/Area Number |
15K09848
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Miyamoto Hiroyuki 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (90312280)
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| Co-Investigator(Kenkyū-buntansha) |
天野 賢治 国立研究開発法人理化学研究所, その他, 研究員 (60333340)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | STXBP1 / MUNC18-1 / シナプス伝達 / てんかん / 攻撃性 / ampakine / intellectual disability / 大田原症候群 / Munc18-1 / Ampakine / Stxbp1 / 大脳基底核 |
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| Outline of Final Research Achievements |
The STXBP1 gene encodes the syntaxin-binding protein 1 that critically controls synaptic transmission. This gene harbors a high frequency of de novo mutations in neurodevelopmental disorders. However, the system and behavioral-level pathophysiological changes caused by these genetic defects remain poorly understood. Constitutional (Stxbp1+/-) mice were subjected to a behavioral test battery examining locomotor activity, anxiety, fear learning, and social interactions including aggression. Stxbp1+/- male mice exhibited enhanced aggressiveness and impaired fear learning. Pharmacological potentiation of the excitatory transmission at active synapses via the systemic administration of ampakine CX516, which enhances the excitatory postsynaptic function, ameliorated the aggressive phenotype of Stxbp1+/- mice. These findings suggest that normalizing the excitatory synaptic transmission is a potential therapeutic option for managing aggressiveness in patients with STXBP1 mutations.
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