Glia in Neurodegenerative Diseases: a Human Glial Chimeric Mouse Model
| Project/Area Number |
22KF0333
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| Project/Area Number (Other) |
21F21410 (2021-2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2021-2022) |
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| Section | 外国 |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Keio University |
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Principal Investigator |
岡野 栄之 慶應義塾大学, 医学部(信濃町), 教授 (60160694)
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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2023: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2022: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2021: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Kii ALS/PDC / iPSC / Astrocytes / MAPT isoforms / Chimeric mouse model / astrocytes |
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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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Report
(2 results)
Research Products
(5 results)
