| 研究課題/領域番号 |
22KF0333
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| 補助金の研究課題番号 |
21F21410 (2021-2022)
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| 研究種目 |
特別研究員奨励費
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| 配分区分 | 基金 (2023)
補助金 (2021-2022) |
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| 応募区分 | 外国 |
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| 審査区分 |
小区分52020:神経内科学関連
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| 研究機関 | 慶應義塾大学 |
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研究代表者 |
岡野 栄之 慶應義塾大学, 医学部(信濃町), 教授 (60160694)
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| 研究分担者 |
LEVENTOUX NICOLAS 慶應義塾大学, 医学部(信濃町), 外国人特別研究員
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| 研究期間 (年度) |
2023-03-08 – 2024-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
2,300千円 (直接経費: 2,300千円)
2023年度: 500千円 (直接経費: 500千円)
2022年度: 1,100千円 (直接経費: 1,100千円)
2021年度: 700千円 (直接経費: 700千円)
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| キーワード | Kii ALS/PDC / iPSC / Astrocytes / MAPT isoforms / Chimeric mouse model / astrocytes |
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| 研究開始時の研究の概要 |
This research investigates whether molecules, typically exosomes from astrocytes, contain proteins or nucleic acids that could contribute to the development of Kii ALS/PDC in neurons, and concerns the engraftment of human progenitors to Rag2-KO pups to improve the chimeric mouse model developed.
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| 研究実績の概要 |
Research aim:
My research targets exosomes from iPSC-derived astrocytes, iPSC differentiation into astrocytes and neurons and engraftment of neural progenitors in mice. The purpose is to investigate in vitro a mechanistic that could explain this peculiar neurodegenerative disease Kii ALS/PDC is, and in vivo to develop a chimeric mouse model which could be used for drugs assays, in order to support research to Kii ALS/PDC-patients.
Research results:
FY2022 has been the year of finalization of the experiments, writing of the article and revisions too. I could successfully visualize in human spinal cord from control-donors a protein paramount for astrocytic-mitochondria respiration and could assess a decrease of it in Kii ALS/PDC-patients. I could also quantify at RNA level a significant decrease in Tau isoforms depending on the clinical stratification of Kii ALS/PDC-patients. I could also differentiate iPSC from 3 healthy donors and 6 patients into several sub-type of neurons using a method published in our Lab (Sato et al. Neurosci Lett 2021). Finally, I have engrafted several NOD/SCID mice with glial progenitors and performed behavioral experiments. After having performed exosomes analysis from iPSC-derived astrocytes, proteome analysis revealed a set of genes indicative of a deleterious effect in iPS-derived Kii ALS/PDC-astrocytes, concomitant with previous published results (article in submission). I also engrafted neural progenitors from 3 control lines and 3 patients and performed behavioral analysis.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Because I'm summarizing my research results about the pathological analysis of Kii ALS/PDC, this research will result in the submission of 2 papers early this final year.
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| 今後の研究の推進方策 |
As this is the final year of this project, the focus will be on the generation of chimeric mouse models, while publishing papers on in vitro research results.
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