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Study on the glutamate-induced spinal neurodysfunction.

Research Project

Project/Area Number 23590113
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionKeio University

Principal Investigator

SUZUKI Takeshi  慶應義塾大学, 薬学部, 准教授 (90187740)

Co-Investigator(Kenkyū-buntansha) KWAK Shin  東京大学, 医学部付属病院, 准教授 (40160981)
SATO Kaoru  国立医薬品食品研究所, 薬理部, 第一室長 (10311391)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords薬理学 / グルタミン酸 / 情報伝達 / 神経変性疾患 / 興奮毒性 / 神経炎症 / ATP / ミクログリア / パロキセチン / 脊髄
Research Abstract

In this study, we investigated mechanisms underlying the dysfunction of glutamate transmission under the inflammatory condition in the spinal cord. We also examined effects of drugs acting on CNS functions. We made in vitro inflammation model using co-culture comprised of astrocytes, microglia and neurons obtained from newborn rat brains. Inflammation decreased glutamate transport by down-regulation of GLAST induced by high-concentration of extracellular glutamate released from activated microglia in this co-culture. Among centrally acting drugs including antidepressants we tested, only paroxetine inhibited the inflammation-induced glutamate release from activated microglia and prevented the decrease in the glutamate transport. We also demonstrated that ATP is one of the factor that made the neural inflammation worse.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (16 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (11 results)

  • [Journal Article] L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation : the 'collusion' hypothesis for increased extracellular L-glutamate concentration in neuroinflammation2013

    • Author(s)
      Takaki J, Fujimori K, Miura M, Suzuki T, Sekino Y, Sato K
    • Journal Title

      Journal of Neuroinflammation

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell-autonomous enhancement of glutamate-uptake by female astrocytes.2012

    • Author(s)
      Morizawa Y, Sato K, Takaki J, Kawasaki A, Shibata K. Suzuki T, Ohta S, Koizumi S.
    • Journal Title

      Cellular and Molecular Neurobiology

      Volume: 32 Pages: 953-956

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] RNA editing of the Q/R site of GluA2 in different cultured cell lines that constitutively express different levels of RNA editing enzyme ADAR2.2012

    • Author(s)
      Yamashita T, Tadami C, Nishimoto Y, Hideyama T, Kimura D, Suzuki T, Kwak S.
    • Journal Title

      Neuroscience Research

      Volume: 73 Pages: 42-48

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the 'collusion' hypothesis for increased extracellular L-glutamate concentration in neuroinflammation.2012

    • Author(s)
      Takaki J
    • Journal Title

      J Neuroinflammation

      Volume: 9 Issue: 1 Pages: 275-275

    • DOI

      10.1186/1742-2094-9-275

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell-autonomous enhancement of glutamate-uptake by female astrocytes.2012

    • Author(s)
      Morizawa, Y
    • Journal Title

      Molecular and Cellular Neurobiology

      Volume: 32 Issue: 6 Pages: 953-956

    • DOI

      10.1007/s10571-012-9829-z

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗うつ薬とP2X4受容体の相互作用の比較検討2014

    • Author(s)
      笠原由佳, 三浦麻利衣, 最上由香里, 関野祐子, 佐藤薫, 鈴木岳之
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] P2X4 receptor -mediated acceleration of microglial activation is important for the L-glutamate release from activated microglia in the early stage of inflammation2013

    • Author(s)
      Sato K, Fujimori K, Takaki J, Suzuki T, Sekino Y
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Paroxetine prevented the activation of microglia by suppressing P2X4 receptor activation2013

    • Author(s)
      Fujimori K, Takaki J, Sato K, Suzuki T
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Paroxetine prevented the activation of microglia by suppressing P2X4 receptor activation.2013

    • Author(s)
      Fujimori K, Takaki J, Sato K, Suzuki T.
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Paroxetine prevents the functional impairment of L-glutamate transporters in inflammation by modulating microglial glutamate release2012

    • Author(s)
      Fujimori K, Takaki J, Sato K, Suzuki T
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Effect of antidepressants on the functional impairment of L-glu transporters under the inflammatory condition2012

    • Author(s)
      Fujimori K, Takaki J, Sato K, Suzuki T
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Paroxetine prevents the functional impairment of L-glutamate transporters in inflammation by modulating microglial glutamate release.2012

    • Author(s)
      Fujimori K, Takaki J, Sato K, Suzuki T.
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] Effect of antidepressants on the functional impairment of L-glu transporters under the inflammatory condition.2012

    • Author(s)
      藤森康希, 高木淳平, 佐藤薫, 鈴木岳之
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] P2X4 receptor-mediated acceleration of microglial activation is important for the L-glutamate release from activated microglia in the early stage of inflammation.

    • Author(s)
      Sato K, Fujimori K, Takaki J, Suzuki T, Sekino Y.
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Neural differentiation potentials in human embryonic stem cell lines.

    • Author(s)
      福本大悟, 松本拓也, 岡田洋平, 末盛博文, 中辻憲夫, 鈴木岳之, 赤松和土, 岡野栄之.
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗うつ薬とP2X4受容体の相互作用の比較検討.

    • Author(s)
      笠原由佳, 三浦麻利衣, 最上由香里, 関野祐子, 佐藤薫, 鈴木岳之.
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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