| Project/Area Number |
21500364
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
KAWAGUCHI Yoshiharu 愛知県心身障害者コロニー発達障害研究所, 発生障害学部, 主任研究員 (00450833)
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| Research Collaborator |
TAKESHIMA Kyoko 愛知県心身障害者コロニー発達障害研究所, 発生障害学部, アルバイト
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 精神疾患 / 不安障害 / 抗うつ / 脱アセチル化酵素 / HDAC6 / ノックアウトマウス / セロトニン神経細胞 / 抗うつ薬 / タンパク質の翻訳後修飾 / アセチル化 / 可逆的アセチル化 / ピルビン酸 / ミトコンドリア / 脱アセチル化 / ドーパミン神経系 / 行動薬理学 / 統合失調症 / ハロペリドール |
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| Research Abstract |
Our previous findings demonstrate that HDAC6-mediated reversible acetylation associates with the mood disorders. To further study and clarify the molecular mechanism how loss of HDAC6 causes emotional arousal, we performed behavioral tests and searched the hyper-acetylated protein(s) in HDAC6 knockout mouse brain. HDAC6 knockout mice showed hyperactivity, less-anxiety, and antidepressant-like behavior. Injection of specific inhibitor of HDAC6 to wild-type mice also induced antidepressant-like behavior, indicating that loss of deacetylase activity of HDAC6 causes abnormal behavior in mice. In HDAC6 knockout mice, the pyruvate dehydrogenase complex was found as a hyper-acetylated protein in brain, and the pyruvate increased in raphe nuclei. Taken together the findings that HDAC6 is well co-localized to serotonergic neurons in raphe nuclei, loss of deacetylate activity of HDAC6 might affect the function of pyruvate dehydrogenase complex, leading to disturb the activity of serotonergic neurons, which in turn, result in emotional arousal in mice.
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