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Elucidating mechanisms of the functional shift toward neuro-toxic astrocyte in amyotrophic lateral sclerosis

Research Project

Project/Area Number 17K14963
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNagoya University

Principal Investigator

Komine Okiru  名古屋大学, 環境医学研究所, 助教 (00456211)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords筋萎縮性側索硬化症 / アストロサイト / 自然免疫 / グリア細胞 / 末梢免疫 / 脳神経疾患 / 神経変性疾患
Outline of Final Research Achievements

To elucidate mechanisms of the functional shift toward neuro-toxic astrocyte in amyotrophic lateral sclerosis, we performed RNA sequencing analyses with magnetic sorted astrocytes from TRIF-deficient and BALB/c background ALS model mouse spinal cords in which a detrimental effect or altered gene expressions in astrocytes were observed. We found that 54 genes including immune functional genes and cell-death-related genes altered in common.

Academic Significance and Societal Importance of the Research Achievements

これまでのALSモデルマウスを用いた研究から運動神経の周囲で活性化したグリア細胞の異常も病態進行に関与することが示されていたが、良いマーカーや解析ツール等の少なさからアストロサイトの毒性転換機構についてはほとんど明らかになっていなかった。本研究によりその一端に関与することが示唆される遺伝子の同定ができたことは学術的に意義があり、これらの遺伝子を標的にした新規治療法の開発にもつながる社会的意義をもつ成果である。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2019 2018 2017 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (15 results) (of which Int'l Joint Research: 5 results) Remarks (2 results)

  • [Journal Article] Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes2018

    • Author(s)
      Komine Okiru、Yamashita Hirofumi、Fujimori-Tonou Noriko、Koike Masato、Jin Shijie、Moriwaki Yasuhiro、Endo Fumito、Watanabe Seiji、Uematsu Satoshi、Akira Shizuo、Uchiyama Yasuo、Takahashi Ryosuke、Misawa Hidemi、Yamanaka Koji
    • Journal Title

      Cell Death & Differentiation

      Volume: 印刷中 Issue: 12 Pages: 2130-2146

    • DOI

      10.1038/s41418-018-0098-3

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intracerebroventricular administration of Cystatin C ameliorates disease in SOD1-linked amyotrophic lateral sclerosis mice2018

    • Author(s)
      Watanabe Seiji、Komine Okiru、Endo Fumito、Wakasugi Keisuke、Yamanaka Koji
    • Journal Title

      Journal of Neurochemistry

      Volume: 145 Issue: 1 Pages: 80-89

    • DOI

      10.1111/jnc.14285

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The multi-dimensional roles of astrocytes in ALS2018

    • Author(s)
      Yamanaka Koji、Komine Okiru
    • Journal Title

      Neuroscience Research

      Volume: 126 Pages: 31-38

    • DOI

      10.1016/j.neures.2017.09.011

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Behavioral characterization of APP knock-in mice model in touchscreen-based tests aiming early detection of Alzheimer's disease.2019

    • Author(s)
      Saifullah MD. Ali Bin、小峯 起、祖父江 顕、山中宏二、溝口博之.
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mice deficient of C-terminal domain of TDP-43 develop age-dependent motor dysfunction via Notch1-Akt signaling pathway.2018

    • Author(s)
      Watanabe S, Nishino K, Matsuoka Y, Jin S, Komine O, Endo F, Tsuiji H, Sakimura K, Mishra A, Yamanaka K.
    • Organizer
      5th RNA Metabolism in Neurological Disease Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Innate immune adaptor TRIF confers neuroprotection in ALS mice by eliminating abnormal astrocytes.2018

    • Author(s)
      Komine O, Yamashita H, Fujimori-Tonou N, Koike M, Jin S, Moriwaki Y, Endo F, Watanabe S, Uematsu S, Akira S, Uchiyama Y, Takahashi R, Misawa H, Yamanaka K.
    • Organizer
      Society for Neuroscience 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intracerebroventricular administration of cystatin C extended the survival time of SOD1G93A mouse model.2018

    • Author(s)
      Watanabe S, Komine O, Endo F, Wakasugi K, Yamanaka K.
    • Organizer
      The29th International Symposium on ALS/MND
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TDP-43C末端ドメイン欠損変異体はNotch1-Akt1シグナル経路を介して加齢依存的な運動障害を引き起こす.2018

    • Author(s)
      渡邊征爾、西野晃平、松岡由理、金 世杰、小峯 起、遠藤史人、築地仁美、﨑村健司、山中宏二.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ALSモデルマウスにおける末梢免疫環境がミクログリア機能に与える影響の解明.2018

    • Author(s)
      小峯 起、大沼周平、池田早織、山中宏二.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高脂肪食の継続投与はグリア細胞の極性変化を伴い視床下部炎症が増悪する.2018

    • Author(s)
      杉山摩利子、坂野僚一、柳沼裕史、滝  啓吾、溝口 暁、恒川 卓、高木博史、伊藤禎浩、小峯 起、山中宏二、有馬 寛.
    • Organizer
      第39回日本肥満学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 早期アルツハイマー病理を呈する患者脳における神経炎症関連遺伝子発現解析.2018

    • Author(s)
      祖父江顕、遠藤史人、小峯 起、村山繁雄、山中宏二.
    • Organizer
      第37回日本認知症学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of roles of glial cell subtypes in hypothalamic inflammation induced by a high fat diet.2017

    • Author(s)
      Sugiyama M, Banno R, Taki T, Mizoguchi A, Tsunekawa T, Takagi H, Ito Y, Komine O, Yamanaka K, Arima H.
    • Organizer
      北米肥満学会(Obesityweek 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Innate immune adaptor TRIF slows disease progression of ALS mice by eliminating aberrantly activated astrocytes.2017

    • Author(s)
      Komine O, Yamashita H. Fujimori-Tonou N, Uematsu S, Akira S, Yamanaka K.
    • Organizer
      28th International symposium on ALS/MND
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ALSモデルマウスのミクログリア機能における末梢免疫の役割2017

    • Author(s)
      小峯  起,大沼周平,池田早織,山中宏二
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 小胞体・ミトコンドリア膜間領域は、筋萎縮性側索硬化症(ALS)の新規治療標的である2017

    • Author(s)
      渡邊征爾,小峯 起,遠藤史人,山中宏二
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Magnetic-activated cell sorting法を用いた視床下部アストロサイトの単離と機能解析2017

    • Author(s)
      杉山摩利子,坂野僚一,滝 啓吾,溝口 暁,恒川 卓,高木博史,伊藤禎浩,小峯 起,山中宏二,有馬 寛
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 筋萎縮性側索硬化症におけるシスタチンCの神経保護効果2017

    • Author(s)
      渡邊征爾,小峯 起,遠藤史人,山中宏二
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] グリオシドGD3によるグリオーマの腫瘍微小環境の制御機構2017

    • Author(s)
      張 璞,大川裕樹,加藤 彰,小峯 起,百田洋之,Robiul Bhuiyan,大海雄介,古川圭子,若林俊彦,岡島徹也,山中宏二,古川鋼一
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Remarks] 環境医学研究所ホームページ

    • URL

      http://www.riem.nagoya-u.ac.jp

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 環境医学研究所病態神経科学分野ホームページ

    • URL

      http://www.riem.nagoya-u.ac.jp/4/mnd/index.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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