Reactive astrocyte-driven epileptogenesis
| Project/Area Number |
18K15701
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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 52050:Embryonic medicine and pediatrics-related
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| Research Institution | University of Yamanashi |
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Principal Investigator |
Sano Fumikzu 山梨大学, 大学院総合研究部, 特任助教 (00622375)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | てんかん / アストロサイト / ミクログリア |
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| Outline of Final Research Achievements |
Extensive activation of glial cells is documented in various central nervous system disorders including epilepsy following status epilepticus (SE). Recent evidence suggests that such activation may represent a cause of subsequent epileptogenesis. Overall, we clearly demonstrate that activation of glial cells in the hippocampus is a cause of epileptogenesis, for which distinct glial cells are activated in a sequential manner; i.e., initial and transient microglial activation with concomitant pro-inflammatory cytokine production induces the appearance of subsequent and lasting astrocytic activation characterized by enhanced IP3R2-mediated Ca2+ signaling. These activated astrocytes eventually enhance seizure susceptibility. Thus, our findings suggest that the therapeutic target to prevent epilepsy after SE should be shifted from microglia (early phase) to astrocytes (late phase).
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| Academic Significance and Societal Importance of the Research Achievements |
けいれん重積発作後に、「グリア細胞」の一種であるアストロサイトが「てんかん原生型アストロサイト」に変化することで、難治てんかんである側頭葉てんかんの発症に関与することを明らかにした。難治てんかんを引き起こす異常なアストロサイト「てんかん原生型アストロサイト」の特徴が明らかとなったことで、これまでの神経細胞を標的とした抗てんかん薬とは全く異なる、新しい抗てんかん薬の開発が進むことが期待される。
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Report
(5 results)
Research Products
(19 results)
