| Project/Area Number |
17K08284
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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 |
Biological pharmacy
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Fut8 / α1,6フコース / ミクログリア / アストロサイト / 神経炎症 / 糖鎖 / ニューロン-グリア相互作用 / AMPA受容体 / 神経科学 / 薬学 |
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| Outline of Final Research Achievements |
α1,6-Fucosyltransferase(Fut8)-deficient (Fut8 KO)mice displayed depresses hippocampal long-term potentiation. Since neuroinflammation is a common pathological change in most brain diseases, this study was focused on investigating the effects of Fut8 in microglia and astrocytes. The number of Iba-1 positive cells and GFAP positive cells were significantly increased in both untreated and lipopolysaccharide stimulated inflammatory Fut8 KO mice by comparison with both wild-type (WT) and hetero Fut8 KO mice. Stimulation with pro-inflammatory factors induced expression levels of fucosylation in primary microglia and astrocytes, as well as in glial cell lines. Cell motility and iNOS expression were easily induced by IFN-γ in Fut8-KO BV-2 cells compared with WT cells.
These results indicated that α1,6-fucosylation may negatively regulate microglia and astrocytes responses to extrinsic stimuli during the process of neuroinflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
α1,6フコースはグリア細胞の活性化の抑制に働くことを明らかにした。Fut8の生体での発現は脳組織で特に高い。それは、グリア細胞の過剰な活性化の抑制に関係しているためと考えられる。ミクログリアやアストロサイトの活性化による炎症反応が神経変性疾患の病態形成に関わることが近年わかってきており、Fut8欠損マウスの表現型の解析により、神経変性疾患の病態形成に糖鎖の視点からの新知見を与えるものである。
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