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The role of D-serine in epilepsy

Research Project

Project/Area Number 22700332
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Neuroscience in general
Research InstitutionUniversity of Toyama

Principal Investigator

INOUE Ran  富山大学, 大学院・医学薬学研究部(医学), 助教 (70401817)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords分子 / 細胞神経科学 / D-セリン / セリンラセマーゼ / NMDA受容体 / てんかん / NDMA受容体
Research Abstract

In this study, we examined the effect of D-serine deficiency on the seizures induced by a single injection of pentylenetetrazole(PTZ) using SR knockout(KO) mice. We found that, compared with wild-type(WT) mice, SR-KO mice showed the attenuation of seizure expression in terms of a significantly shortened duration of generalized seizures and resistance to generalized clonic-tonic seizures. Consistently, immunohistochemical analysis of c-Fos demonstrated that the level of c-Fos labeling induced by high-dose PTZ in the cerebral cortex, hippocampal CA1, hippocampal CA3, and the basolateral nucleus of the amygdala in WT mice was significantly higher than that in SR-KO mice. Moreover, PTZ induced an increase in extracellular glutamate level in the dentate gyrus of WT mice at two different time phases. However, such a PTZ-induced increase in glutamate level was completely inhibited in SR-KO mice. The present findings suggest that SR may be a target for the development of new therapeutic strategies for epileptic seizures.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (14 results)

All 2012 2011 2010 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (5 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine2012

    • Author(s)
      Horio M., Kohno M., Fujita Y., Ishima T., Inoue R., Mori H., Hashimoto K.
    • Journal Title

      PLoS One

      Volume: 7

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Levels of D-serine in the brain and peripheral organs of serine racemase(Srr) knock-out mice2011

    • Author(s)
      Horio M., Kohno M., Fujita Y., Ishima T., Inoue R., Mori H., Hashimoto K.
    • Journal Title

      Neurochem. Int

      Volume: 59 Pages: 583-589

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Levels of D-serine in the brain and peripheral orcans of serine racemase (Srr)knock-out mice2011

    • Author(s)
      Horio M., Kohno M., Fujita Y., Ishima T., Inoue R., Mori H., Hashimoto K.
    • Journal Title

      Neurochem.Int.

      Volume: 59 Pages: 853-859

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential regional distribution of phosphorylated tau and synapseloss in the nucleus accumbens in tauopathy model mice.2011

    • Author(s)
      Kambe T, Motoi Y, Inoue R, Kojima N, Tada N, Kimura T, Sahara N, Yamashita S, Mizoroki T, Takashima A, Shimada K, Ishiguro K, Mizuma H, Onoe H, Mizuno Y, Hattori N
    • Journal Title

      Neurobiology of Disease

      Volume: 42 Pages: 404-414

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serine racemase knockout mice2010

    • Author(s)
      Mori H., Inoue R.
    • Journal Title

      Chemistry & Biodiversity

      Volume: 7 Pages: 1573-1578

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serine racemase knockout mice.2010

    • Author(s)
      Mori H, Inoue R
    • Journal Title

      Chemistry & Biodiversity

      Volume: 7 Pages: 1573-1578

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] ペンチレンテトラゾール誘発痙攣発作におけるD-セリンの機能解析2011

    • Author(s)
      井上蘭,原井朋美,藤田有子,田中亜由美,堀尾茉央,橋本謙二,森寿
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Presentation] セリンラセマーゼノックアウトマウスではペンチレンテトラゾール急性投与により誘発される痙攣発作に関連した変化が抑制される2011

    • Author(s)
      井上蘭,原井朋美,藤田有子,田中亜由美,堀尾茉央,橋本謙二,森寿
    • Organizer
      D-アミノ酸研究会学術講演会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Pentylenetetrazole-induced seizure is attenuated in serine racemase knockout mice2011

    • Author(s)
      井上蘭, 原井朋美, 藤田有子, 田中亜由美, 堀尾茉央, 橋本謙二, 森寿
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report
  • [Presentation] Pentylenetetrazole-induced seizure is attenuated in serine racemase knockout mice2010

    • Author(s)
      Ran Inoue
    • Organizer
      Society For Neuroscience's 40th annual meeting
    • Place of Presentation
      San Diego, California, USA
    • Year and Date
      2010-11-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pentylenetetrazole-induced seizure is attenuated in serine racemase knockout mice2010

    • Author(s)
      Inoue R., Harai T., Hashimoto K., Tanaka A., Mori H.
    • Organizer
      Society For Neuroscience's 40th annual meeting
    • Place of Presentation
      San Diego, USA
    • Related Report
      2011 Final Research Report
  • [Book] 「seriesモデル動物利用マニュアル」疾患モデルの作製と利用-脳・神経疾患,セリンラセマーゼ欠損マウス2011

    • Author(s)
      井上蘭,森寿
    • Publisher
      株式会社エル・アイ・シー
    • Related Report
      2011 Final Research Report
  • [Book] Serine racemase knockout mice. D-Amino Acids in Chemistry, Lifesciences, and Biotechnology2010

    • Author(s)
      Mori H., Inoue R.
    • Publisher
      Lifesciences, and Biotechnology
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://bsd.neuroinf.jp/wiki/%E3%82%BB%E3%83%AA%E3%83%B3%E3%83%A9%E3%82%BB%E3%83%9F%E5%8C%96%E9%85%B5%E7%B4%A0

    • Related Report
      2011 Final Research Report

URL: 

Published: 2010-08-23   Modified: 2016-04-21  

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