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An Exploratory research on biomarkers of depression based on astrocyte-derived exosomes

Research Project

Project/Area Number 18K07620
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kure Medical Center

Principal Investigator

Okada-Tsuchioka Mami  独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, 研究員(移行) (30517280)

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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsエクソソーム / アストロサイト / うつ病 / トランスレーショナルリサーチ / 精神神経科学
Outline of Final Research Achievements

In this study, we focused on astrocyte-derived exosomes (AST-exosomes) as targets for biomarker of depression. We have found a promising antibody for quantifying and purifying AST-exosomes. No changes in AST-exosome levels were observed in the brain of disease model and treatment-responsive model for depression. Therefore, we have constructed a method for purifying AST-exosomes using magnetic beads on which the specific antibody is immobilized, and are currently proceeding with the analysis of exosomal cargo. On the other hand, the amount of AST-exosomes in human plasma is very small, and further studies are considered necessary for quantification and purification. In an alternative study, we found that total exosome levels may be altered in the plasma of depressed patients and depression model mice.

Academic Significance and Societal Importance of the Research Achievements

これまでに末梢血を用いてバイオマーカーの探索研究が行われてきたが、末梢由来の因子が多く含まれているために脳内の変化のみを捉えることが困難であった。この問題を解決するために、末梢血中における脳内の変化を反映する成分を使えないかと考えてASTエクソソームに着目した。既に報告されているものとは異なる有望なアストロサイト系膜表出タンパクを見出すことができ、脳の総エクソソーム中からASTエクソソームを精製することにも成功した。ヒト血漿中においても微量であるが同定することができている。今回の研究成果はさらなる高感度化への条件検討や技術開発への発展につながる可能性が考えられる。

Report

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

    (12 results)

All 2020 2019 2018 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (3 results) Remarks (2 results)

  • [Journal Article] Lysophosphatidic acid induces thrombospondin‐1 production in primary cultured rat cortical astrocytes2020

    • Author(s)
      Hisaoka‐Nakashima Kazue、Yokoe Toshiki、Watanabe Shintaro、Nakamura Yoki、Kajitani Naoto、Okada‐Tsuchioka Mami、Takebayashi Minoru、Nakata Yoshihiro、Morioka Norimitsu
    • Journal Title

      Journal of Neurochemistry

      Volume: in press Issue: 4 Pages: 849-864

    • DOI

      10.1111/jnc.15227

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential anatomical and cellular expression of lysophosphatidic acid receptor 1 in adult mouse brain2020

    • Author(s)
      Kajitani Naoto、Okada-Tsuchioka Mami、Kano Kuniyuki、Omori Wataru、Boku Shuken、Aoki Junken、Takebayashi Minoru
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 531 Issue: 2 Pages: 89-95

    • DOI

      10.1016/j.bbrc.2020.05.068

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased Matrix Metalloproteinases in Cerebrospinal Fluids of Patients with Major Depressive Disorder and Schizophrenia2020

    • Author(s)
      Omori Wataru、Hattori Kotaro、Kajitani Naoto、Okada-Tsuchioka Mami、Boku Shuken、Kunugi Hiroshi、Okamoto Yasumasa、Takebayashi Minoru
    • Journal Title

      International Journal of Neuropsychopharmacology

      Volume: 23 Issue: 11 Pages: 713

    • DOI

      10.1093/ijnp/pyaa049

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased serum levels of thrombospondin‐1 in female depressed patients2019

    • Author(s)
      Okada‐Tsuchioka Mami、Omori Wataru、Kajitani Naoto、Shibasaki Chiyo、Itagaki Kei、Takebayashi Minoru
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 40 Issue: 1 Pages: 39-45

    • DOI

      10.1002/npr2.12088

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shared preventive factors associated with relapse after a response to electroconvulsive therapy in four major psychiatric disorders.2019

    • Author(s)
      Omori Wataru、Itagaki Kei、Kajitani Naoto、Abe Hiromi、Okada‐Tsuchioka Mami、Okamoto Yasumasa、Takebayashi Minoru
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 印刷中 Issue: 8 Pages: 494-500

    • DOI

      10.1111/pcn.12859

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antidepressant amitriptyline‐induced matrix metalloproteinase‐9 activation is mediated by Src family tyrosine kinase, which leads to glial cell line‐derived neurotrophic factor mRNA expression in rat astroglial cells.2019

    • Author(s)
      Abe Hiromi、Kajitani Naoto、Okada‐Tsuchioka Mami、Omori Wataru、Yatsumoto Masahide、Takebayashi Minoru
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 印刷中 Issue: 3 Pages: 156-163

    • DOI

      10.1002/npr2.12055

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced Serum and Cerebrospinal Fluid Levels of Autotaxin in Major Depressive Disorder2019

    • Author(s)
      Itagaki Kei、Takebayashi Minoru、Abe Hiromi、Shibasaki Chiyo、Kajitani Naoto、Okada-Tsuchioka Mami、Hattori Kotaro、Yoshida Sumiko、Kunugi Hiroshi、Yamawaki Shigeto
    • Journal Title

      International Journal of Neuropsychopharmacology

      Volume: 22 Issue: 4 Pages: 261

    • DOI

      10.1093/ijnp/pyz005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 血清トロンボスポンジン-1(TSP-1)は女性うつ病患者において減少する2020

    • Author(s)
      岡田麻美、大盛 航、梶谷直人、柴崎千代、板垣 圭、町野彰彦、竹林 実
    • Organizer
      第50回日本神経精神薬理学会年会 第42会日本生物学的精神医学会年会 第4回日本精神薬学会総会・学術集会 NPBPPP2020合同年会 ONLINE
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血清トロンボスポンジン-1(TSP-1)は女性うつ病患者において減少する2019

    • Author(s)
      岡田麻美、大盛 航、梶谷直人、柴崎千代、板垣 圭、町野彰彦、竹林 実
    • Organizer
      第38回躁うつ病の薬理・生化学的研究懇話会
    • Related Report
      2019 Research-status Report
  • [Presentation] グリアにおける抗うつ薬受容体としてのLPA1の可能性-抗うつ薬のLPA1への直接作用に関する検討-2018

    • Author(s)
      岡田麻美、宮野加奈子、梶谷直人、安部裕美、大盛 航、板垣 圭、上園保仁、竹林 実
    • Organizer
      第5回サイコグリア研究会
    • Related Report
      2018 Research-status Report
  • [Remarks] 国立病院機構呉医療センター・中国がんセンター 臨床研究部

    • URL

      http://kure.hosp.go.jp/department/clinical_research/

    • Related Report
      2019 Research-status Report
  • [Remarks] 国立病院機構呉医療センター・中国がんセンター 精神科

    • URL

      http://kure.hosp.go.jp/department/psychiatry/

    • Related Report
      2019 Research-status Report

URL: 

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

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