Exploring the novel role of mitochondrial dynamics in schizophrenia
| 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 |
岩田 圭子 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 | oligodendrocyte / mitochondria / 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 Annual Research Achievements |
In this project, we wish to address the impact of changes in mitochondrial biogenesis on central nervous system (CNS) development (especially the oligodendrocyte differentiation) and animal behavior.
Here, we report new findings from the 1st to 4rd year of the project as follows;
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. We were planning to use oligodendrocyte-specific Pgc1-1alpha KO mice for in vivo analyses. However, since the expression of Cre driven by the oligodendrocyte-specific promoter in the purchased mice was not observed, we are currently conducting validation of these mice and discussing with the vendor. Therefore, experiments in vivo could not be conducted.
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Report
(5 results)
Research Products
(17 results)
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[Journal Article] Dietary spermidine improves cognitive function2021
Author(s)
Schroeder S, Hofer SJ, Zimmermann A, Pechlaner R, Dammbrueck C, Pendl T, Marcello GM, Pogatschnigg V, Bergmann M, Muller M, Gschiel V, Ristic S, Tadic J, Iwata K,......Racz B, Kiechl S, Eisenberg T, Madeo F.
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Journal Title
Cell Reports
Volume: 35
Issue: 2
Pages: 108985-108985
DOI
Related Report
Peer Reviewed / Open Access
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