| Project/Area Number |
21791121
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | University of Fukui |
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Principal Investigator |
OMATA Naoto University of Fukui, 医学部附属病院, 講師 (30334832)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 気分安定薬 / GSK3β / 歯状回 / 抗うつ効果 / 神経毒性 / グルコース代謝 / ミトコンドリア機能 / ポジトロン / バルプロ酸 / リチウム / レンチウイルス / RNAi / 脳スライス / NSAIDs / 神経保護 / アラキドン酸 |
|---|
| Research Abstract |
The mechanism of clinical action of valproate was investigated through its inhibitory action against glycogen synthase kinase 3β (GSK3β). Inhibition of GSK3β in the hippocampal dentate gyrus of experimental animal revealed the antidepressive effect in the forced swim test and tail suspension test. Therefore, the inhibitory action of valproate against GSK3β might contribute to the mechanism of its clinical action. Next, the mechanism of the side effect induction of valproate in the central nervous system was investigated through its direct effect against the brain mitochondrial function. In the experiment using brain slices made from experimental animals, valproate decreased the mitochondrial function. Therefore, the inhibition of the mitochondrial function by valproate might contribute to its side effect in the central nervous system.
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