2021 Fiscal Year Annual Research Report
Glia in Neurodegenerative Diseases: a Human Glial Chimeric Mouse Model
| Project/Area Number |
21F21410
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| Allocation Type | Single-year Grants |
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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) |
2021-09-28 – 2024-03-31
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| Keywords | Kii ALS/PDC / astrocytes / MAPT isoforms |
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| Outline of Annual Research Achievements |
I included more control-iPast samples to strengthen the RNA-seq data. We confirmed the relevance of one gene involved in the mitochondrial respiratory chain, which leads us to consider a direct role of astrocytes in the development of the pathology. We also investigated, using human brain samples, the ratio 3R/4R of MAPT transcription by ddPCR and found that in Kii-ALS, patients have a ratio value less than 1. This result needs to be confirmed using biofluids and would be useful for patient stratification.
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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
Our research on the Kii disease will result in the submission of 2 papers before the end of the calendar year. The paper on the generation of Kii-iPast cells only requires confirmation of the transcription of a few genes by RT-qPCR from the experimental point of view as well as finalization of the Gene Ontology. The paper on MAPT isoforms will be submitted after the WB have been finalised, a few experimental conditions remain to deal with.
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| Strategy for Future Research Activity |
We want to study the co-culture of Kii-iPast with neurons to investigate the effect of these patients’ astrocytes on neuron survival. I am currently in the process of generating neurons using well established protocols from the Laboratory, but still have to investigate cell culture impact on cell viability. The transplantation of neurospheres into the brains of NOD/SCID mice remains to be organised. Until now, the Rag2-/- pups and mice appeared as too fragile to survive long enough post engraftment. The neurospheres are currently frozen.
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Research Products
(3 results)
