| Project/Area Number |
19K08041
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Wakayama Medical University (2022-2023)
University of Fukui (2019-2021) |
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Principal Investigator |
Keiko Iwata 和歌山県立医科大学, 薬学部, 講師 (30415088)
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| Co-Investigator(Kenkyū-buntansha) |
松崎 秀夫 福井大学, 子どものこころの発達研究センター, 教授 (00334970)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | mitochondria / oligodendrocyte / differentiaion / schizophrenia / oligodendrocye |
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| Outline of Research at the Start |
Abnormal energy metabolisms are reported in brains of schizophrenia (SZ). Mitochondria have a central role in energy metabolisms and significant reduction of mitochondria mass in oligodendrocytes have been observed in SZ brains. PGC-1 alpha is a key regulator of mitochondrial biogenesis. In a set of preliminary experiments, we hypothesize that PGC-1 alpha plays a crucial role in oligodendrocyte differentiation via regulating mitochondrial biogenesis and involved in pathophysiology of SZ. Here, we propose our project to verify this hypothesis.
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| Outline of Final Research Achievements |
We identified the novel variant of PGC-1alpha, a transcriptional coactivator, which is a key regulator of mitochondrial biogenesis and was involved in oligodendrocyte differentiation using the human oligodendrocyte cell line. The variant was expressed in the human brain. We performed RNA sequences using human brain samples. (The study was Fukui University Medical Research Ethics Committee (approval no.2020028).) The expression of the variant was correlated with 2 transcriptional receptors which were involved in cell differentiation. We established the primary culture system of oligodendrocytes at Wakayama Medical Univ and confirmed that the expression of the novel variant was increased during the differentiation of the mouse oligodendrocyte precursor cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、中枢神経系の発達に関連する脳科学の分野にとって重要であるだけでなく、精神疾患の生物学的基盤を理解する上でも重要である。長年にわたり、神経細胞とシナプスが神経科学の主要な焦点となっており、精神疾患の病態生理に関する理論に影響を与えてきた。しかし脳内の細胞の大部分は神経細胞ではなく、グリア細胞である。本研究では、ミトコンドリアによって制御されるオリゴデンドロサイトの分化が、高次脳機能や統合失調症の病態生理にどのように影響するかに焦点を当てた。本研究で得られた結果は、統合失調症を含む精神疾患の病因・病態解明の一助になる可能性がある。
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