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A novel mice model of MSA by overexpression of mutant alpha-synuclein in oligodendroglia in a temporarily restrictive manner using Tet-off system

Research Project

Project/Area Number 18K07501
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionKyushu University

Principal Investigator

Matsuse Dai  九州大学, 医学研究院, 助教 (70596395)

Co-Investigator(Kenkyū-buntansha) 山口 浩雄  九州大学, 大学病院, 特任講師 (00701830)
雑賀 徹  九州大学, 医学研究院, 共同研究員 (00744880)
山崎 亮  九州大学, 医学研究院, 准教授 (10467946)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords多系統萎縮症 / グリア炎症 / ミクログリア / バイオマーカー / intermediate monocytes / αシヌクレイン / オリゴデンドログリア / 脱髄 / CSF1R阻害薬 / トランスジェニックマウス
Outline of Final Research Achievements

We generated a transgenic mice model which express mutant human A53Tα-synuclein in oligodendroglia as a new animal model of multiple system atrophy MSA). This will be a useful mice model because it develops clinical symptoms and pathological changes within a few months. Behavioral analysis and pathological evaluation were performed. Marked activation of microglia was seen especially in early stage. Therapeutic approaches were also analyzed.
We also analyzed about the biomarkers of MSA from peripheral blood of patients. Early decrease of peripheral blood intermediate monocytes may be characteristic of MSA.

Academic Significance and Societal Importance of the Research Achievements

任意の時期にαシヌクレインをオリゴデンドロサイトに発現できる、多系統萎縮症の新規モデルを作成した。髄鞘形成後の時期からαシヌクレインを発現させることができ、従来のモデルよりMSAの病態に近く、また短期間での評価が可能なため、病態の解明や治療薬の開発に有用である。
多系統萎縮症患者の末梢血解析では、単球系の細胞分画の特徴を新たに見出すことができ、本疾患のバイオマーカーとして有用のみならず、本疾患のさらなる病態の解明にもつながると思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2021 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Early decrease in intermediate monocytes in peripheral blood is characteristic of multiple system atrophy-cerebellar type2020

    • Author(s)
      Dai Matsuse, Ryo Yamasaki, Guzailiayi Maimaitijiang, Hiroo Yamaguchi, Katsuhisa Masaki, Noriko Isobe, Takuya Matsushita, Jun-ichi Kira
    • Journal Title

      Journal of Neuroimmunology

      Volume: 349 Pages: 577395-577395

    • DOI

      10.1016/j.jneuroim.2020.577395

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] オリゴデンドロサイト特異的αシヌクレイン蓄積による小脳型多系統萎縮症モデルの樹立2021

    • Author(s)
      松瀬大, 山口浩雄, 眞﨑勝久, 西村由宇慈, 田中辰典, 雑賀徹, 田中謙二, 山﨑亮, 吉良潤一
    • Organizer
      第14回日本パーキンソン病・運動障害疾患学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Early decrease of peripheral blood intermediate monocytes in multiple system atrophy cerebellar-type.2020

    • Author(s)
      Matsuse Dai, Yamasaki Ryo, Maimaitijiang Guzailiayi, Yamaguchi Hiroo, Kira Jun-ichi
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Therapeutic drug search using model mice for multiple system atrophy and primary progressive multiple sclerosis.2020

    • Author(s)
      Tanaka Tatsunori, Nishimura Yuji, Masaki Katsuhisa, Matsuse Dai, Yamaguchi Hiroo, Saiga Toru, Watanabe Mitsuru, Yamasaki Ryo, Tanaka Kenji, Kira Jun-ichi
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Gene expression profile of multiple system atrophy/primary progressive multiple sclerosis mice model.2020

    • Author(s)
      Yamaguchi Hiroo, Tanaka Tatsunori, Matsuse Dai, Nishimura Yuji, Masaki Katsuhisa, Saiga Toru, Watanabe Mitsuru, Yamasaki Ryo, Tanaka Kenji, Kira Jun-ichi
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新規小脳型多系統萎縮症モデルによる脱髄・神経細胞障害機序とグリア制御による新規治療法開発の試み2020

    • Author(s)
      西村由宇慈, 眞﨑勝久, 松瀬大, 山口浩雄, 雑賀徹, 田中辰典, 田中謙二, 山﨑亮, 岩城徹, 吉良潤一
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A novel model of primary progressive multiple sclerosis by oligodendroglial mutant alpha-synuclein2019

    • Author(s)
      Toru Saiga, Hiroo Yamaguchi, Dai Matsuse, Katsuhisa Masaki, Yiwen Cui, Ryo Yamasaki, Kenji Tanaka, Jun-ichi Kira
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Presentation] A novel mice model of PPMS/MSA by oligodendroglial overexpression of mutant alpha-synuclein2019

    • Author(s)
      Dai Matsuse, Hiroo Yamaguchi, Toru Saiga, Katsuhisa Masaki, Yiwen Cui, Ryo Yamasaki, Kenji Tanaka, Jun-ichi Kira
    • Organizer
      第42回日本神経科学大会/第62回日本神経化学会大会
    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Presentation] A novel model of multiple system atrophy-cerebellar type and primary progressive multiple sclerosis2019

    • Author(s)
      Katsuhisa Masaki, Dai Matsuse, Hiroo Yamaguchi, Toru Saiga, Yuji Nishimura, Tatsunori Tanaka, Mitsuru Watanabe, Ryo Yamasaki, Kenji Tanaka, Jun-ichi Kira
    • Organizer
      The 24th Annual Meeting of the Japan Glia
    • Related Report
      2019 Research-status Report
  • [Presentation] オリゴデンドロサイト特異的αシヌクレイン蓄積による小脳型多系統萎縮症・一次進行型多発性硬化症モデル2019

    • Author(s)
      真崎勝久、松瀬大、山口浩雄、雑賀徹、西村由宇慈、田中辰典、渡邉充、田中謙二、山﨑亮、吉良潤一
    • Organizer
      第31回日本神経免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Expression of mutant α-synuclein in oligodendrocytes induces remarkable glial inflammation and demyelination in the spinal cord and brainstem/cerebellar white matter: A novel model of multiple system atrophy-cerebellar type and primary progressive multiple sclerosis2019

    • Author(s)
      Hiroo Yamaguchi, Dai Matsuse, Katsushisa Masaki, Toru Saiga, Yuji Nishimura, Mitsuru Watanabe, Ryo Yamasaki, Kenji Tanaka, Jun-ichi Kira
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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