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Elucidation of the effects of impaired glucose tolerance in the brain on postoperative cognitive dysfunction and establishment of its preventive methods

Research Project

Project/Area Number 18K08833
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionHimeji Dokkyo University

Principal Investigator

Yamamoto Naoki  姫路獨協大学, 薬学部, 教授 (90393157)

Co-Investigator(Kenkyū-buntansha) 祖父江 和哉  名古屋市立大学, 医薬学総合研究院(医学), 教授 (90264738)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords糖尿病 / 麻酔薬 / 術後認知機能 / 炎症 / 術後認知機能障害 / 2型糖尿病 / 吸入麻酔薬
Outline of Final Research Achievements

1. In the type 2 DM model TSOD mice, we investigated the activation of insulin-related intracellular signal transduction system in order to confirm the abnormal glucose tolerance in the mice before administration of inhalation anesthetic. As a result, it was found that the PI3 kinase pathway, which is one of the insulin signal transduction systems of the whole brain, decreases with aging. We are currently reassessing cognitive decline after inhalational anesthetic administration using a new object recognition test and a Y-maze test.
2. It was found that it regulates in astrocytes (primary culture) on the expression of neprilysin and insulin degrading enzymes, which are Aβ-degrading enzymes, by activating the signals of protein kinases A and C, which play important roles in the intracellular signal transduction system in the brain. It was also clarified that this regulated expression also regulates the degradation of Aβ by astrocytes. (Neurosci Res. 2020)

Academic Significance and Societal Importance of the Research Achievements

アジア系人種の特徴を有する2型糖尿病(DM)モデルのTSOD(Tsumura Suzuki Obese Diabetes)マウスに吸入麻酔薬を投与することによって、脳全体のインスリンシグナル伝達系の一つであるPI3kinase経路が低下しており、この経路の下流にはアルツハイマー病発症に大きく関わるタウタンパクのリン酸化の調節機構がある。この結果によって、吸入麻酔薬投与後の脳内耐糖能異常とPOCDの因果関係を解明する手がかりを掴めると考える。

Report

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

    (7 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results) Presentation (4 results)

  • [Journal Article] Protein kinases A and C regulate amyloid-β degradation by modulating protein levels of neprilysin and insulin-degrading enzyme in astrocytes2020

    • Author(s)
      Yamamoto N, Nakazawa M, Nunono N, Yoshida N, Obuchi A, Tanida M, Suzuki K, Ikeda-Matsuo Y, Sobue K.
    • Journal Title

      Neurosci Res

      Volume: 166 Pages: 62-72

    • DOI

      10.1016/j.neures.2020.05.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Central Injection of Leptin Increases Sympathetic Nerve Outflows to the Stomach and Spleen in Anesthetized Rats.2019

    • Author(s)
      Tanida M, Iwasaki Y, Yamamoto N.
    • Journal Title

      In Vivo

      Volume: 33 Issue: 6 Pages: 1827-1832

    • DOI

      10.21873/invivo.11675

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Insulin-signaling Pathway Regulates the Degradation of Amyloid β-protein via Astrocytes.2018

    • Author(s)
      Yamamoto N, Ishikuro R, Tanida M, Suzuki K, Ikeda-Matsuo Y, Sobue K.
    • Journal Title

      Neuroscience

      Volume: 385 Pages: 227-236

    • DOI

      10.1016/j.neuroscience.2018.06.018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] アストロサイト発現ネプリライシンはpoly I:Cによる発現低下によってアミロイドβ蛋白の分解を抑制する2020

    • Author(s)
      山本直樹、徳門巧也、大渕絢子、谷田守、松尾由理、祖父江和哉
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] アストロサイト発現ネプリライシンはpoly I:Cによって発現低下がもたらされる2019

    • Author(s)
      山本直樹、徳門巧也、大渕絢子、谷田守、松尾由理、祖父江和哉
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Insulin regulates expression of neprilysin and IDE in cultured astrocytes2018

    • Author(s)
      Yamamoto N, Ishikuro R, Tanida M, Suzuki K, Sobue K.
    • Organizer
      第61回日本神経化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] PKAおよびPKC経路とアストロサイトのネプリライシンとインスリン分解酵素発現検討2018

    • Author(s)
      山本直樹、祖父江和哉
    • Organizer
      第37回日本認知症学会学術集会
    • Related Report
      2018 Research-status Report

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

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