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 |
Section | 一般 |
Review Section |
Basic Section 52030:Psychiatry-related
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Research Institution | Wakayama Medical University (2022) University of Fukui (2019-2021) |
Principal Investigator |
岩田 圭子 和歌山県立医科大学, 薬学部, 講師 (30415088)
|
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)
|
Project Period (FY) |
2019-04-01 – 2024-03-31
|
Project Status |
Granted (Fiscal Year 2022)
|
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)
|
Keywords | oligodendrocyte / mitochondria / schizophrenia / oligodendrocye |
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 oligodendrocyte differentiation) and animal behavior. Neurons and synapses have long been the dominant focus of neuroscience, informing theories on the pathophysiology of psychiatric disorders. However, the majority of cells in the brain are not neurons but glial cells. We are performing experiments to address how oligodendrocyte differentiation regulated by mitochondria impacts the higher brain functions and pathophysiology of schizophrenia (SZ) following our research methodology and approach. Here, we report new findings by the 4th 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. Now we are conducting in vivo and in vitro experiments using mice. 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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Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
As we planned, 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. On the other hand, we could not visit the Lab of CR (Prof. Scorrano), Padova University, Italy, and conduct experiments, especially mitochondrial analyses using imaging systems that are available in his Lab, these experiments are a little behind schedule.
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Strategy for Future Research Activity |
I will visit the Lab of CR (Prof. Scorrano), Padova University, Italy, and conduct experiments following the original plan.
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