| Project/Area Number |
23249060
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | The Institute of Physical and Chemical Research |
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Principal Investigator |
YOSHIKAWA TAKEO 独立行政法人理化学研究所, 脳科学総合研究センター, チームリーダー (30249958)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kazuo 独立行政法人理化学研究所, 脳科学総合研究センター, 副チームリーダー (10322695)
MAEKAWA Motoko 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (50435731)
HAMASAKI Kei 富山大学, 大学院・医学薬学研究部(医学), 助教 (50533494)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥47,840,000 (Direct Cost: ¥36,800,000、Indirect Cost: ¥11,040,000)
Fiscal Year 2013: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2012: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2011: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
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| Keywords | 統合失調症 / 神経発達障害仮説 / マウス / 多価不飽和脂肪酸 / オリゴデンドロサイト / ミエリン / 転写因子 / DNAメチル化 / 必須脂肪酸 / 脳発達期 / 遺伝子発現 / 発症予防 / GABA / ネルボン酸 / ステアリン酸 / GABA含有ニューロン |
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| Research Abstract |
One of the cogent hypotheses of schizophrenia etiology is
"neurodevelopmental abnormality theory", which proposes that subtle insults during brain developmental period"underlies the susceptibility of schizophrenia. We tested this theory by raising mice with polyunsaturated fatty acid (PUFA)-deficient diet during neurodevelopmental stage (PUFA(-)-mice). The PUFA(-)-mice displayed behavioral phenotypes reminiscent of early stage of schizophrenia. Interestingly, myelin-related genes were down-regulated in the frontal cortex of PUFA(-)-mice as in the postmortem brains of schizophrenia. We revealed that the above downregulations are caused by decreased expressions of transcription factor genes, TF-A and TF-B. The promoter regions of TF-A and TF-B from the brains of PUFA(-)-mice showed elevated DNA methylation, which probably lead to the lowered expressions of TF-A and TF-B.
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