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Clarification and prevention of novel mechanisms of cognitive impairment in patients with metabolic syndrome

Research Project

Project/Area Number 17K01886
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionNational Defense Medical College

Principal Investigator

Ishizuka Toshiaki  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 薬理学, 教授 (30399117)

Co-Investigator(Kenkyū-buntansha) 佐藤 泰司  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 生化学, 教授 (10505267)
野村 さやか  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 薬理学, 助教 (20791651)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsインフラマソーム / ミクログリア / 脳内炎症 / TNF / LPS / 神経前駆細胞 / 神経分化 / 認知機能障害 / IL-1beta / IL-18 / メタボリック・シンドローム / 神経新生 / サイトカイン
Outline of Final Research Achievements

Treatment of microglia or neural progenitor cells with LPS and TNF induces inflammasome activation and supresses differentiation of neural progenitor cells into neural cells. In addition, feeding of a high fat diet for 16 weeks and injection of LPS for 5 days in male C57BL/6 mice may induce inflammasome activation of microglia and attenuate neurogenesis and cognitive function.

Academic Significance and Societal Importance of the Research Achievements

近年の疫学的研究により、メタボリックシンドロームが血管性認知症だけでなくアルツハイマー型認知症の危険因子であることが報告されているが、その病態機序はこれまで未解明であった。今回の研究により、メタボリックシンドロームが認知機能障害をもたらす機序に関して、ミクログリアのインフラマソーム活性化による脳内炎症の誘導と、それに伴い起きる神経新生障害が認知機能低下につながる可能性が示唆された。これより、メタボリックシンドロームへの積極的な治療介入や抗炎症作用を持つ神経新生促進薬の研究が認知症の新たな予防・治療法の開発につながることが期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (22 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Low body mass index and lymphocytopenia associate with Mycobacterium avium complex pulmonary disease in patients with rheumatoid arthritis.2019

    • Author(s)
      Hirose W, Harigai M, Uchiyama T, Itoh K, Ishizuka T, Matsumoto M, Nanki T.
    • Journal Title

      Modern Rheumatology

      Volume: 29 Issue: 1 Pages: 105-112

    • DOI

      10.1080/14397595.2018.1452334

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular hydrogen prevents social deficits and depression-like behaviours induced by low-intensity blast in mice.2018

    • Author(s)
      Satoh Y, Araki Y, Kashitani M, Nishii K, Kobayashi Y, Fujita M, Suzuki S, Morimoto Y, Tokuno S, Tsumatori G, Yamamoto T, Saitoh D, Ishizuka T.
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 77 Issue: 9 Pages: 827-836

    • DOI

      10.1093/jnen/nly060

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment.2018

    • Author(s)
      Maruta K, Watanabe C, Hozumi H, Kurihara C, Furuhashi H, Takajo T, Okada Y, Shirakabe K, Higashiyama M, Komoto S, Tomita K, Nagao S, Ishizuka T, Miura S, Hokari R.
    • Journal Title

      J Leukoc Biol

      Volume: 104 Issue: 5 Pages: 1013-1022

    • DOI

      10.1002/jlb.3a0717-304r

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of muscarinic acetylcholine receptor stimulation on the differentiation of mouse induced pluripotent stem cells into neural progenitor cells.2018

    • Author(s)
      Ishizuka T, Ozawa A, Katsuura M, Nomura S, Satoh Y.
    • Journal Title

      Clin Exp Pharmacol Physiol

      Volume: 45 Issue: 11 Pages: 1198-1205

    • DOI

      10.1111/1440-1681.12993

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor growth limited to subcutaneous site vs tumor growth in pulmonary site exhibit differential effects on systemic immunities.2017

    • Author(s)
      Masuda J, Takayama E, Strober W, Satoh A, Morimoto Y, Honjyo Y, Ichinose T, Tokuno SI, Ishizuka T, Nakata T, Mizutani A, Umemura N, Kitani A, Fuss IJ, Shigehiro T, Kawaki H, Mizuno-Kamiya M, Kondoh N, Seno M.
    • Journal Title

      Oncol Rep

      Volume: 38 Issue: 1 Pages: 449-455

    • DOI

      10.3892/or.2017.5646

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Discovery of small molecules that induce the degradation of Huntingtin.2017

    • Author(s)
      Tomoshige S, Nomura S, Ohgane K, Hashimoto Y, Ishikawa M
    • Journal Title

      Angew Chem

      Volume: 129 Pages: 11688-11691

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Effects of transrepression-selective liver X receptor ligands on inflammasome activation of microglia and neural progenitor cells.2020

    • Author(s)
      Ishizuka T, Takahashi S, Goda W, Makishima M, Ishikawa M, Hashimoto Y.
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Molecular hydrogen as therapeutic medical gas for nervous disease.2020

    • Author(s)
      Satoh Y, Ishizuka T.
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アデノシンデアミナーゼの神経保護作用の解明に向けて2020

    • Author(s)
      太田 宏之、田村 吏沙、荒毛 将史、守本 祐司、石塚 俊晶
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ミクログリアおよび神経前駆細胞のインフラマソーム活性化に対するTransrepression作用選択的なLXRリガンドの影響2019

    • Author(s)
      石塚 俊晶、高橋 さやか、合田 和香美、槇島 誠、石川 稔、橋本 祐一
    • Organizer
      第6回 サイコグリア研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 探索行動テストのための24時間型オペラント箱の開発2019

    • Author(s)
      太田 宏之、荒毛 将史、宝田 悠、佐鳥 久仁朗、高橋 達二、守本 祐司、石塚 俊晶
    • Organizer
      第141回 日本薬理学会関東部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Effects of inflammasome activation on proliferation and differentiation of neural progenitor cells2019

    • Author(s)
      Ishizuka T, Ozawa A, Nomura S, Satoh Y.
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] The role of BK channels in spinal microglia for the induction of neuropathic pain in mice.2019

    • Author(s)
      Satoh Y, Morohashi T, Hayashi Y, Itakura S, Kawaguchi M, Nakanishi H, Ishizuka T.
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effects of inflammasomes on differentiation of neural progenitor cells into neural cells.2018

    • Author(s)
      Ishizuka Toshiaki, Ozawa Ayako, Nomura Sayaka, Yasushi Satoh
    • Organizer
      ISSCR 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Activation of inflammasomes in neural progenitor cells inhibits differentiation into neural cells.2018

    • Author(s)
      Ishizuka Toshiaki, Ozawa Ayako, Nomura Sayaka, Yasushi Satoh
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of transrepression-selective liver X receptor ligands.2018

    • Author(s)
      Nomura S, Umeda K, Makishima M, Hashimoto Y, Ishizuka T, Ishikawa M.
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transrepression作用選択的なLiver X受容体リガンドの創製と腸管新生作用の検討2018

    • Author(s)
      野村さやか、梅田香織、槇島誠、橋本祐一、石塚俊晶、石川稔
    • Organizer
      第36回ヒト細胞学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effects of oxidized low density lipoprotein on proliferation or differentiation of mouse neural progenitor cells into neural cells2017

    • Author(s)
      Ishizuka Toshiaki, Ozawa Ayako, Nomura Sayaka, Yasushi Satoh
    • Organizer
      ISSCR 2017 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Education and Research of Basic Medical Sciences in National Defense Medical College (NDMC)2017

    • Author(s)
      Toshiaki Ishizuka
    • Organizer
      2nd International Conference of Military Medical Schools 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 関節リウマチ患者の肺 MAC 症合併に関連する因子 の検討:横断研究からの報告2017

    • Author(s)
      廣瀬 恒, 内山 隆司, 針谷 正祥, 伊藤 健 司, 石塚 俊晶, 松本 光世, 南木 敏宏
    • Organizer
      第61 回日本リウマチ学 会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 幼少期の全身麻酔薬曝露と自閉症スペクトラム障害の関連2017

    • Author(s)
      嶋田 哲也、佐藤 泰司、神尾 陽子、赤井 亮介、風間 富栄、石塚 俊晶
    • Organizer
      第136回日本薬理学会関東部会
    • Related Report
      2017 Research-status Report
  • [Book] Regulation of signal transduction in human cell research. (Chapter 2: Role of the receptor-mediated signaling pathways on the proliferation and differentiation of pluripotent stem cells.)2018

    • Author(s)
      Ishizuka T (edited by Shinomiya N, Kataoka H, Xie Q)
    • Publisher
      Springer
    • ISBN
      9789811072956
    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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