| Project/Area Number |
20591364
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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 |
Psychiatric science
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 精神薬理学 / エピジェネティクス / てんかん / 扁桃体 / ヒストンアセチル化 / 甲状腺ホルモン受容体 / HDAC抑制剤 / ドーパミン / セロトニン / 聴原性てんかん / ヒストン修飾 / バルプロ酸 / 小脳 / 海馬 |
|---|
| Research Abstract |
Although numerous causes of forming epileptic focus have been implicated, the mechanism by which intrinsic properties of neuronal activity would change to pathological neuroexitability in neuronal circuits remains to be elucidated. Epigenesis engages in the development, functional differentiation, neurogenesis, and plasticity of cell signaling. This study was aimed to elucidate the epigenetic changes related to occurrence of seizure and potential therapeutic targets in the refractory epilepsy using the following two animal models : Noda epileptic rats, hippocampus of which was studied in the previous research of KAKEN, and thyroid hormone receptor(TR) deficient mice, a possible model of audiogenic seizure with auditory dysfunction. As results of experiments using TR-mutant mice, it was demonstrated that region-specific modifications of epigenetic status, associated with alterations of catecholaminergic metabolisms. In particular, TRss-/-mice have low dopamine metabolisms in the caudate/putamen and in the accumbens. The 5-HT metabolism was also decreased in the amygdala, associated with increases of histone deacethylase(HDAC)-2 and-3 expressions. Manipulation of HDAC function may be a possible therapeutic approrch to neuropsychatric disorders including epilepsy.
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