| Project/Area Number |
16K19634
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | University of Yamanashi |
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Principal Investigator |
Fumikazu SANO 山梨大学, 大学院総合研究部, 特任助教 (00622375)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | てんかん / ミクログリア / アストロサイト / 神経炎症 / 脳神経疾患 / 神経科学 |
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| Outline of Final Research Achievements |
The aim of this study is to test our hypothesis that early microglial activation after status epilepticus (SE) lead to reactive astrocytes which can cause epileptogenesis.
We detected a significant increase in the area of Iba1-positive microglia, mRNA of TNF-α in the hippocampus at 1 day after SE which was followed by the increase in the area of GFAP-positive astrocyte in CA1 from 7 to 28 days after SE. Astrocytes displayed significantly larger and longer Ca2+ signals from 25 to 32 days after SE. In addition, less dose of pilocarpine was required for the induction of the second SE at 28 days after the first SE. Microglia inhibition with minocycline reduced astrogliosis, Ca2+ signals of astrocytes, and rescued the increased seizure-susceptibility. These results suggest that reactive astrocytes triggered by activated microglia undergo a part of physiological changes which can cause epilepstogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究を通じて、てんかん原生獲得の分子病態におけるグリア相互作用（活性化ミクログリアが誘導するアストロサイトの活性化）の関与が明らかとなったことで、既存のてんかん治療薬とは全く異なる、グリア細胞を標的とした新たなてんかん治療薬開発の基盤となる成果となりうる。また、これらの結果は、従来の難治てんかんに対する「単にてんかん発作を抑制する」という対症療法的な治療戦略と異なりてんかん原生そのものを予防・消失させるという「てんかんに対する病態修飾治療」という新たな治療戦略の基礎的概念の確立と、臨床応用にむけた萌芽的な研究成果となりうる。
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