| Project/Area Number |
16K08442
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Osaka University |
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Principal Investigator |
Inagaki Shinobu 大阪大学, 連合小児発達学研究科, 特任研究員 (90151571)
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| Co-Investigator(Kenkyū-buntansha) |
土江 伸誉 兵庫医療大学, 共通教育センター, 講師 (00434879)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | Sema4D / microglia / oligodendrocyte / development / ischemic injury / NO / polyamine / Erk1/2 / ミクログリア / iNOS / アルギナーゼ / ポリアミン / 脳梗塞傷害 / IFN-β / オリゴデンドロサイト / 活性化ミクログリア / 脳虚血傷害 / セマフォリン / 発達 / Arginase / semaphorin / 解剖学 / 発生・分化 / 脳 / グリア細胞 / 髄鞘形成 |
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| Outline of Final Research Achievements |
In this study, we studied how Sema4D contributes to microglia and oligodendrocyte development and to their interrelation. During postnatal development, microglia were not affected in number by the absence of Sema4D, but their M1-type activation was partially inhibited in some brain area. In vitro studies, Sema4D upregulated NO (nitric oxide) production by microglia cultured under LPS stimulation, and increased cell death of oligodendrocytes and decreased number of oligodendrocytes differentiated from the progenitor cells. The absence of Sema4D increased polyamine content and production of microglia and injured tissue, suggesting that this promoted proliferation and restoration of oligodendrocytes after ischemic injury. We suggested a new mechanism of inhibitory effect of Sema4D deficiency on NO production via IFN-β and partial inhibition of Erk1/2 signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
ミクログリアは脳居住型組織マクロファージで、脳の炎症・傷害へ素早く対応し、炎症の悪化や修復に貢献するのみならず、脳の髄鞘形成の発達にも関与する。Sema4Dは発達期のオリゴデンドロサイトに発現するばかりでなく、活性化したミクログリアにも発現し、ミクログリアの活性化の制御やオリゴデンドロサイトの発達や髄鞘形成の制御に関与し傷害後の脳の修復に関与すること、ならびにその機序の一端を示すことができた。ミクログリアの活性化や髄鞘の修復は様々な脳の疾患に関わるので、Sema4Dの抑制により脳疾患の修復に貢献できる可能性が考えられる。
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