| Project/Area Number |
23659571
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Psychiatric science
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| Research Institution | 公益財団法人東京都医学総合研究所 (2012)
Tokyo Metropolitan Organization for Medical Research (2011) |
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Principal Investigator |
TATEBAYASHI Yoshitaka 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 副参事研究員 (80342814)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 気分障害 / 大うつ病 / 双極性障害 / オリゴデンドロサイト / オリゴデンドロサイト前駆細胞 / 脂肪酸 / 統合失調症 / 死後脳 / ミエリン |
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| Research Abstract |
Neuropsychiatric disorders such as major depressive disorder (MDD) are highly prevalent and contribute substantially to disease burden worldwide. However, exploring the etiologies of MDD, especially those related to the neural circuits, cell types, and brain areas, involves substantial challenges. We have tackled these challenges by developing novel methodologies to analyze unfixed frozen postmortem brains from patients with MDD and from normal controls. We found in the frontopolar cortex (FPC; Brodmann Area 10 (BA10)) that MDD is associated both with a significant reduction in the densities of oligodendroglial cells, and with abnormal fatty acid (FA) composition all of which was aggravated in a myelin level-dependent manner. These results raise the distinct and novel possibilities that BA10 is involved in a key neural circuit responsible for and that oligodendroglial cells are the particular cell types affected in MDD. In the present study, using cultured adult rat hippocampal oligodendrocyte progenitor cells (OPCs), we have challenged to establish a novel cell model of MDD especially regarding FA metabolism. We have found that a growth factor dose-dependently may be able to reproduce the FA metabolic abnormalities found in the MDD brains.
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