Vulnerability of cerebellar and cerebral cortical neurons in neurodegenerative diseases
| Project/Area Number |
18H02535
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 46020:Anatomy and histopathology of nervous system-related
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 神経変性疾患 / iPS細胞 / 脊髄小脳変性症 / プルキンエ細胞 / 大脳神経 / 細胞脆弱性 / 神経分化 / 小脳プルキンエ細胞 / 大脳 / 小脳 |
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| Outline of Final Research Achievements |
Spinocerebellar ataxias (SCAs) are genetically heterogeneous group of autosomal dominantly inherited progressive disorders. Most SCA cause prominent damage to cerebellar Purkinje cells with consecutive cerebellar atrophy, whereas Purkinje cells are only mildly affected in some SCAs. To investigate differences of cell vulnerability in SCAs, we differentiated Purkinje cells and non-Purkinje cells, such as cortical neurons or motor neurons, from SCA patient-derived iPS cells. We examined cell type specific vulnerabilities utilizing histological analysis and transcriptome analysis combination with perturbation of culture conditions. We observed a certain type of SCA derived Purkinje cells revealed robustness whereas other SCA-derived Purkinje cells were fragile in morphological changes.
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| Academic Significance and Societal Importance of the Research Achievements |
神経変性疾患を引き起こす原因遺伝子の変異は数多く同定されているが、神経が変性に至るメカニズムは不明なことが多い。本課題では、病型ごとに変性する細胞が異なる原因を研究するため、患者由来のiPS細胞を用いて、病気でダメージを受ける細胞を作製し、これを様々な条件で培養することにより、何が細胞の脆弱性に関与しているのかを調べたものである。本実験の結果、培養条件が多少悪くてもダメージを受けない細胞がいること、通常なら問題にならない程度の条件でもダメージを受けやすい細胞がいることを明らかにすることができた。神経変性疾患で特定の細胞のみが影響を受ける機序を解明するin vitroモデルになると考えられる。
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Report
(4 results)
Research Products
(13 results)
