Elucidation of pathophysiology of refractory depression and development of newer treatment based on the disturbance of spine dynamics
| Project/Area Number |
20591368
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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 | Hiroshima University |
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Principal Investigator |
MORINOBU Shigeru Hiroshima University, 大学院・医歯薬学総合研究科, 准教授 (30191042)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 難治性うつ病 / 脳由来神経栄養因子 / 樹状突起スパイン / マイクロRNA / 海馬 / 母子分離 / 学習性無力 / trkB受容体 / BDNF / MeCP2 / miR-132 / miR-30a / miR-141 / miR-200a / IMK-1 / microRNA / スパイン / うつ病 / LIMK-1 |
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| Research Abstract |
The present study was undertaken to examine whether the decreased synaptic density through the spine abnormality in the hippocampus is involved in the pathophysiology of refractory depression. We developed a rat model of refractory depression using neonatal isolation and learned helplessness. The principal findings of this study were that 1) the spine length of dendritic spines was longer in the hippocampus of the model rats without any changes in spine density, 2) the immunoreactivity of brain-derived neurotrophic factor (BDNF) was decreased, 3) the levels of microRNA (miR)-132 were decreased, 4) the levels of miR-134 were not affected, 5) the immunoreactivity of TrkB was decreased. These findings suggested that the spine abnormality due to the decreased BDNF-TrkB signal in the hippocampus may be involved in the pathophysiology of refractory depression, with less contribution by downregulation of BDNF through miR regulation from the 3' region of the BDNF gene.
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Report
(4 results)
Research Products
(25 results)
