Project/Area Number |
24500453
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
|
Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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)
|
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, 実験補助
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | HDAC6 / セロトニン / 抗うつ / 脱アセチル化 / ピルビン酸 / ノックアウトマウス / 情動障害 / ドーパミン / マウス行動実験 / ミトコンドリア / 脱アセチル化酵素 / 抗うつ薬 |
Outline of Final Research Achievements |
Our major goal is to provide a new aspect of understanding psychiatric diseases. To address this issue, we focus HDAC6 knockout mice that show hyperactivity, less anxiety, and antidepressant-like behavior. In this study, we found the disturbance of neuronal activity in both serotonergic and dopaminergic neurons in HDAC6 KO mouse brain by evaluating the amount of monoamines, tryptophan hydroxylase, and dopamine D2 receptor. We also found that loss of deacetylate activity induces the accumulation of pyruvate accompanied by the reduction in ATP in raphe and PC12 cells, suggesting energy disability in serotonergic neurons in HDAC6 KO mice. Our findings demonstrate that deacetylate activity of HDAC6 might contribute to maintain the proper function in energy metabolism in serotonergic neurons, and its disturbance affects neuronal activity, leading to emotional arousal in mice.
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