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A study on pathogenesis of depression by focusing on pathogenesis-specific reactive astrocytes

Research Project

Project/Area Number 18K15534
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionKumamoto University (2019)
Department of Clinical Research, National Hospital Organization Kure Medical Center (2018)

Principal Investigator

Kajitani Naoto  熊本大学, 大学院生命科学研究部(医), 特別研究員 (60755742)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアストロサイト / LPA1受容体 / 反応性アストロサイト / うつ病
Outline of Final Research Achievements

This study aims to investigate the hypothesis that there are pathospecific reactive astrocytes in Major depressive disorder (MDD).
Micorarray analysis revealed that long-term treatment with antidepressants did not alter reactive astrocyte-specific genes in the mouse brain.
Previous study found that the LPA1 receptor in astrocytes is an important receptor for antidepressant effects. Then the current study explored the cellular distribution pattern of LPA1 receptor in the mouse brain. The current findings demonstrated that LPA1 receptor-expressing cells in the adult brain were mainly oligodendrocytes and astrocytes and suggested that S100B-positive astrocytes are a subpopulation of astrocytes that may be involved in the MDD.

Academic Significance and Societal Importance of the Research Achievements

うつ病は、自殺の主な原因であり、社会的損失が大きな疾患である。また、既存の治療法では再発率も高く、根治に向けた病態解明が望まれている。本研究ではうつ病の病態解明を行うために、中枢神経系の半数近くを構成するアストロサイトに着目し、病態への関与を検討した。研究の結果、抗うつ薬の効果に関与する受容体(LPA1)が特定のアストロサイトに存在することが明らかとなった。今後、特定したアストロサイトをより詳細に検討することで、この細胞を標的にしたうつ病治療薬やバイオマーカーの開発につながる可能性が考えられる。

Report

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

    (12 results)

All 2020 2019 2018 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 2 results) Remarks (3 results)

  • [Journal Article] Differential anatomical and cellular expression of lysophosphatidic acid 1 receptor in adult mouse brain.2020

    • 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: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research 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
  • [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] 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
  • [Presentation] Distribution of multiple lysophosphatidic acid receptors in adult mouse brain2019

    • Author(s)
      Kajitani N,Okada-Tsuchioka M,Abe H,Omori W,Itagaki K,Machino A,Takebayashi M.
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳内における抗うつ薬受容体(LPA1)発現細胞の特定とその役割2018

    • Author(s)
      梶谷直人、岡田麻美、安部裕美、大盛 航、板垣 圭、竹林 実
    • Organizer
      第5回サイコグリア研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 抗うつ薬受容体(LPA1)の脳内発現とその役割2018

    • Author(s)
      梶谷直人、岡田麻美、安部裕美、大盛 航、板垣 圭、竹林 実
    • Organizer
      第37回躁うつ病の薬理・生化学的研究懇話会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cellular localization of lysophosphatidic acid receptor 1 in the mouse brain.2018

    • Author(s)
      Naoto Kajitani, Mami Okada-Tsuchioka, Hiromi Abe, Wataru Omori, Kei Itagaki, Minoru Takebayashi
    • Organizer
      Neuroscience 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 熊本大学大学院生命科学研究部神経精神医学講座

    • URL

      https://www.kumamoto-neuropsy.jp/

    • Related Report
      2019 Annual Research 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

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

    • Related Report
      2019 Annual Research 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 精神科

    • URL

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

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2021-02-19  

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