| Project/Area Number |
17K01975
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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 |
Basic / Social brain science
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| Research Institution | Shinshu University |
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Principal Investigator |
Mori Takuma 信州大学, 学術研究院医学系, 助教 (70545798)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | X染色体不活性化 / シナプスバランス異常 / 自閉症 / Neuroligin / CASK / ガンマオシレーション / 抑制性シナプス / シナプス / 興奮抑制バランス / 神経回路 |
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| Outline of Final Research Achievements |
I used CASK heterogenous knockout mice as a model animals of autism spectrum disorder and analyzed synaptic functions using electrophysiological methods. We recorded neurons in acute brain slices, including somatosensory cortex, of CASK heterogeneous knockout mice using patch clamp recording and analyzed synaptic inputs. We found that the frequency of excitatory synaptic inputs was increased and that that of inhibitory synaptic inputs was decreased in CASK heterogeneous knockout mice. As reported in other ASD model mice, an imbalance of excitatory and inhibitory synaptic inputs were observed in CASK heterogeneous knockout mice and the expression of NMDA receptor 2B subunit by CASK is indicated as a molecular mechanism of the synaptic imbalance.
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| Academic Significance and Societal Importance of the Research Achievements |
自閉症は１００人あたり１人が報告されており、男性が女性のおよそ４倍の発生頻度であることから、実験動物を用いた基礎研究でもオス動物を用いた実験がほとんどであった。本研究はメス動物を用いた研究であり、発展の目覚ましい自閉症研究の知見を活用し、その適用範囲を拡大できる研究と言える。また、発達期の神経機能成熟に関わるNMDA受容体の関与を示したことは、CASK遺伝子欠損だけでなく、NMDA受容体の関わる遺伝子異常のシナプス機能異常への波及効果も期待できる。
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