2023 Fiscal Year Final Research Report
Analyzing oligodendrocyte-neuron interaction using a rabies virus vector and AAV vectors
| Project/Area Number |
21K15197
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46020:Anatomy and histopathology of nervous system-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | オリゴデンドロサイト / 髄鞘 / 小脳 / プルキンエ細胞 / ウイルスベクター |
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| Outline of Final Research Achievements |
We have combined attenuated rabies virus and tissue clearing techniques to determine the type of axons that are myelinated by single cerebellar oligodendrocytes . This approach revealed that approximately half of adult oligodendrocytes myelinate on Purkinje cell axons and that more than 90% of cells selectively myelinate axons of Purkinje cells during mouse early development(Battulga et al., BioRxiv, 2023). We also clarified the mechanism of gene leakage, which is a major problem for using Cre-dependent expression vectors (Osanai et al., Mol Ther Methods Clin Dev, in press, 2024).
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| Free Research Field |
神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
小脳は運動機能や認知機能に重要な役割を持つ。プルキンエ細胞は小脳皮質における唯一の出力細胞であり、今回我々はこの細胞が発生の初期に選択的に髄鞘形成されていることを突き止めた(Battulga et al., BioRxiv, 2023)。
遺伝子治療では標的細胞のみに遺伝子を発現させるのが理想だが、実際にはリークと呼ばれる標的外での遺伝子発現がみられる(Osanai et al., Mol Ther Methods Clin Dev, in press, 2024)。我々はこのメカニズムの一端を解明した。本研究により、近い将来標的細胞のみを破壊するような遺伝子治療が開発できると考えられる。
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