| Project/Area Number |
17K07108
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 細胞骨格 / 学習 / 記憶 |
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| Outline of Final Research Achievements |
Discrimination among different spatial contexts depends on the hippocampal dentate gyrus (DG). However, molecular basis remains unclear. Here we find that Septin-null (Sept-KO) mice retain memory of spatial context for 2h, but not for 24h, in spatial pattern separation test. To narrow down brain regions responsible for the cognitive impairment, we conduct local subacute depletion of SEPT from the bilateral DG of wild-type mice, and local supplementation of SEPT into the bilateral DG of KO mice, which respectively recapitulates and rescues the defect. The perforant path-DG synapses in KO mice are normal, except for a significant scarcity of smooth endoplasmic reticulum (sER), a Ca2+ reservoir in dendritic spines. The sER anomaly is recapitulated by SEPT depletion from primary cultured rat DG granule cells (DGCs). The DGC-selective requirement of SEPT will illuminate a novel gating or translocation mechanism that regulates the entry of sER from dendritic shaft into spines.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、学術的には細胞小器官の移動が記憶保持に影響を及ぼすことを示す初めての概念となる。社会的には、認知症患者と診断される数年前の時点でも空間pattern separation機能が低下することが報告されていることから、空間弁別課題の長期記憶保持の基盤となる分子メカニズムの解明は薬剤探索や記憶保持機能低下を抑制する食品の開発に繋がることが期待できる。
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