Role of alpha1,6-fucosyltransferase Fut8 in neuron-glia interactions

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08284
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Fukuda Tomohiko 東北医科薬科大学, 薬学部, 准教授 (40433510)
• Project Period (FY): 2017-04-01 – 2020-03-31
• 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

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.

Free Research Field

糖鎖生物学

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。