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Creation of preventive / delayed medical technology for the onset of schizophrenia targeting ADAM10

Research Project

Project/Area Number 17K10293
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Mikawa Sumiko  浜松医科大学, 医学部, 助教 (70359743)

Co-Investigator(Kenkyū-buntansha) 植木 孝俊  名古屋市立大学, 医薬学総合研究院(医学), 教授 (60317328)
Project Period (FY) 2017-04-01 – 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 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords統合失調症 / ミクログリア / ADAM10 / NMRプローブ / MRI / 精神病理学
Outline of Final Research Achievements

In the present study magnetic resonance imaging (MRI) switching probe was newly developed to visualize in vivo under MRI the activity of pathological proteinase, ADAM10, which generates soluble fractalkine (FKN) from membrane bound form of FKN. The production of soluble FKN in the co-culture system of neuron and microglia was quantitatively analyzed according to the principle of paramagnetic relaxation, where MRI switching probe was originally designed and synthesized. And here the brain slice culture system derived from rodent model of schizophrenia was used to comprehensively analyze gene expression pattern in microglia at the onset of inflammation. As the results a series of molecules associated with the activation of microglia were identified.

Academic Significance and Societal Importance of the Research Achievements

統合失調症は、思春期前後に発症し、幻覚妄想、自発性欠如や感情鈍磨、認知機能障害を呈し社会機能の障害を残す進行性の精神疾患である。近年、我々は頭部専用ポジトロン断層撮影(PET)を用いて、統合失調症患者の脳では広汎な部位でミクログリアが活性化していることを明らかにした。本研究では、統合失調症の培養脳スライスモデルを調製し、そこでの炎症反応の生起に伴うミクログリアでの遺伝子発現変化を解析することによって、ミクログリアの活性化に関与する脳内因子を同定した。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results)

  • [Journal Article] Follistatin expression in the central nervous system of the adult rat2020

    • Author(s)
      Ogawa C, Misawa S, Yamashita K, Hayashi Y, Masumoto K, Katou F, Sato K
    • Journal Title

      Journal of Chemical Neuroanatomy

      Volume: 105 Pages: 101753-101753

    • DOI

      10.1016/j.jchemneu.2020.101753

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased Proliferation in the Neurogenic Niche, Disorganized Neuroblast Migration, and Increased Oligodendrogenesis in Adult Netrin-5-Deficient Mice2020

    • Author(s)
      Ikegaya Shunsuke、Iga Yurika、Mikawa Sumiko、Zhou Li、Abe Manabu、Sakimura Kenji、Sato Kohji、Yamagishi Satoru
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 570974-570974

    • DOI

      10.3389/fnins.2020.570974

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BMP expression in the adult rat central nervous system2019

    • Author(s)
      Hayashi Y, Mikawa S, Ogawa C, Masumoto K, Katou F, Sato K.
    • Journal Title

      J Chem Neuroanat.

      Volume: 98 Pages: 41-54

    • DOI

      10.1016/j.jchemneu.2019.03.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed

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Published: 2017-04-28   Modified: 2022-01-27  

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