| Project/Area Number |
26293326
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Juntendo University |
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Principal Investigator |
Arai Hajime 順天堂大学, 医学部, 教授 (70167229)
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| Co-Investigator(Kenkyū-buntansha) |
中島 円 順天堂大学, 医学部, 准教授 (50317450)
宮嶋 雅一 順天堂大学, 医学部, 准教授 (60200177)
菅野 秀宣 順天堂大学, 医学部, 准教授 (90265992)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | 糖タンパク質 / 認知機能障害 / トランスジェニックマウス / パッチクランプ / 認知機能 / 特発性正常圧水頭症 / 加齢 / 髄液診断 / 脳脊髄液 / 神経毒性蛋白 / 認知障害 / 加齢性蛋白 / 興奮性シナプス後場電位 / 長期増強 / 認知症 / 動物モデル / 正常圧水頭症 / 長期増強現象 / LRG1 |
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| Outline of Final Research Achievements |
To investigate the relationship between LRG expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (Tg) focusing on hippocampus.
Immunostaining and western blotting revealed age-related increase of LRG expression in hippocampal neuron . Y-maze and Morris water maze test indicated spatial memory was retained in 24-week-old Tg, while deteriorated in 48-week-old compared to age-matched controls. Field excitatory postsynaptic potential declined in Tg compared to controls in 8, 24, and 48-week-old, obviously with age. Paired-pulse ratio decreased with age in Tg, while increased in controls. As a result, long-term potentiation was retained in 8 and 24-week-old Tg while diminished in 48-week-old comparing with age-matched controls. Electron-microscopic observation revealed decrease of synaptic vesicles and junctions in Tg. Hippocampal LRG overexpression contributes to synaptic dysfunction, which lead to memory impairment with advance of age.
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