| Project/Area Number |
16K20888
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Anesthesiology
Neurochemistry/Neuropharmacology
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Research Collaborator |
UENO shinya
SHIMOYAMA shuji
NIKAIDO yoshikazu
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | benzodiazepine / diazepma / Lcn2 / diazepam / ベンゾジアゼピン / lipocalin2 / GABA受容体 / 認知機能 / GABAA受容体 / 向精神薬 / ジアゼパム |
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| Outline of Final Research Achievements |
In this study, to investigate the effect of chronic benzodiazepine (BZD) on cognitive dysfunction, memory behavior, spine density of hippocampal neuron, and LTP of hippocampus were examined in chronic diazepam (DZP, aBZD) treated young and mice. The behavior test indicated that chronic DZP treatment impaired retrieval of aged mice. In DZP-treated groups, the spine density of hippocampal pyramidal neurons was reduced in CA1 and CA3 of aged mice and CA1 of young mice. The CA1 LTP was reduced by chronic DZP treatment in young mice but not in aged mice. These results suggested that chronic DZP treatment might decrease spine density of CA3 neuron in hippocampus, and thus impaired retrieval performance in aged mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果から、ベンゾジゼピン系薬剤であるジアゼパム（DZP）の長期使用は老齢マウスの海馬神経細胞のスパインを減少させ、認知機能を低下させる可能性が示唆された。一方、若齢マウスではDZP長期投与による海馬LTPやスパイン密度への影響は認められたものの、認知機能行動には有為な低下は認められなかった。これらの結果は、DZP長期投与の認知機能への影響は加齢に伴って変遷することを示すものであり、学術的にも興味深い。今後、本研究結果をもとにDZP長期投与による認知機能低下の予防法や治療法の開発へ発展させることで、社会的に貢献することができると考えられる。
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