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Functional and Phenotypic Regulation of GABAergic Development with Neurotrophic Factors

Research Project

Project/Area Number 22300107
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionNiigata University

Principal Investigator

NAWA Hiroyuki  新潟大学, 脳研究所, 教授 (50183083)

Co-Investigator(Kenkyū-buntansha) NAMBA Hisaaki  新潟大学, 脳研究所, 助教 (90332650)
Co-Investigator(Renkei-kenkyūsha) OZAKI Miwako  早稲田大学, 生命医療工学研究所, 教授 (30291058)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2012: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2010: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
KeywordsGABA / 神経栄養因子 / 脳発達 / 大脳皮質 / 基底核 / 上皮成長因子 / ニューレグリン / 神経発達 / シナプス可塑性 / 脳疾患 / シナプス
Research Abstract

GABAergic neurons play crucial roles in the brain functions, attenuating excitatoryneurotransmission, generating oscillation activity patterns, and regulating developmentalplasticity and critical periods. Recently, we implicate neurotrophic factors of the EGFfamily in the brain diseases of developmental origin such as autism and schizophrenia. Inthe present project, we planed to explore the physiological activity, cellular signaling, and pathologic contribution of EGF-like factors’ actions on GABAergic neurons and theirsubtype(s). Among various subtypes of cortical GABAergic neurons, parvalbumin-positiveGABA neurons carried ErbB4 and reacted with neuregulin-1. This factor elevated theexpression of AMPA-type glutamate receptors, more efficiently derived GABA release, andproduced stronger postsynaptic inhibition. The same type of GABAergic neurons expressedErbB1 and responded to EGF as well, although the direction of the reaction was totallyopposite; EGF down-regulated the glutamate receptor levels and glutamate aciddecarboxylase expression, provoking more modest inhibition in postsynaptic neurons. Incontrast, the same factor, EGF, exerted a distinct action on pallidal GABA neurons; itelevated the excitability of these neurons and enabled those to release more amounts ofGABA in the target region. Therefore, these findings suggest that GABAergic neurons inthe brain harbor dynamic plasticity to react with EGF-like factors but the direction andmagnitude of the phenotypic responses differ significantly depending on individualsubtypes of GABAergic neurons.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (17 results)

All 2013 2012 2011 2010

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (7 results) Book (1 results)

  • [Journal Article] ErbB1-4-dependentEGF/neuregulin signals and their crosstalk in the central nervous system:pathological implications in schizophreniaand Parkinson's disease2013

    • Author(s)
      Iwakura Y, Nawa H
    • Journal Title

      Front CellNeurosci

      Volume: 7 Pages: 4-4

    • Related Report
      2012 Final Research Report
  • [Journal Article] Exposure to the cytokine EGF leads to abnormalhyperactivity of pallidal GABA neurons:implications for schizophrenia and itsmodeling2013

    • Author(s)
      Sotoyama H, Namba H, Chiken S,Nambu A, Nawa H
    • Journal Title

      J Neurochem

    • Related Report
      2012 Final Research Report
  • [Journal Article] Exposure to the cytokine EGF leads to abnormal hyperactivity of pallidal GABA neurons: implications for schizophrenia and its modeling.2013

    • Author(s)
      Sotoyama H
    • Journal Title

      J Neurochem

      Volume: 未定 Issue: 4 Pages: 518-528

    • DOI

      10.1111/jnc.12223

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: pathological implications in schizophrenia and Parkinson's disease.2013

    • Author(s)
      Iwakura Y
    • Journal Title

      Front Cell Neurosci

      Volume: 7 Pages: 4-4

    • DOI

      10.3389/fncel.2013.00004

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Experimentalschizophrenia models in rodentsestablished with inflammatory agents andcytokines2012

    • Author(s)
      Nawa H, Yamada K
    • Journal Title

      Methods Mol Biol

      Volume: 829 Pages: 445-451

    • Related Report
      2012 Final Research Report
  • [Journal Article] Neuregulin-1 signals from theperiphery regulate AMPA receptorsensitivity and expression in GABAergicinterneurons in developing neocortex2011

    • Author(s)
      Abe Y, Namba H, Kato T, Iwakura Y,Nawa H
    • Journal Title

      JNeurosci

      Volume: 31(15) Pages: 5699-5709

    • Related Report
      2012 Final Research Report
  • [Journal Article] In vitro production ofan active neurotrophic factor, neuregulin-1:qualitative comparison of different cell-freetranslation systems2011

    • Author(s)
      Wang R, Iwakura Y, Araki K, SotoyamaH, Takei N, Nawa H
    • Journal Title

      Neurosci Lett

      Volume: 497(2) Pages: 90-93

    • Related Report
      2012 Final Research Report
  • [Journal Article] In vitro production of an active neurotrophic factor, neuregulin-1 : qualitative comparison of different cell-free translation systems2011

    • Author(s)
      Wang R, Iwakura Y, Araki K, Sotoyama H, Takei N, Nawa H
    • Journal Title

      Neurosci Lett

      Volume: 497 Issue: 2 Pages: 90-93

    • DOI

      10.1016/j.neulet.2011.04.036

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuregulin-1 signals from the periphery regulate AMPA receptor sensitivity and expression in GABAergic Interneurons in Developing Neocortex2011

    • Author(s)
      Y. Abe, 他4名
    • Journal Title

      The Journal of Neuroscience

      Volume: 31 印刷中

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Pallidal hyperdopaminergicinnervation induced by neonatal exposureto epidermal growth factor; implication inschizophrenia2012

    • Author(s)
      Nawa H, Namba H, Iwakura Y, Takei N, Sotoyama H
    • Organizer
      The 11^<th> Biennial Metting of APSN
    • Place of Presentation
      Kobe JAPAN.
    • Related Report
      2012 Final Research Report
  • [Presentation] Neurotrophic interaction of midbrain dopaminergicneurons with EGF and neuregulin-1;implication in schizophrenia2012

    • Author(s)
      Nawa H, Iwakura Y
    • Organizer
      The Bit's 3rdAnnual World Congree of NeuroTalk-2012
    • Place of Presentation
      Beijin CHINA.
    • Related Report
      2012 Final Research Report
  • [Presentation] Pallidal hyperdopaminergic innervation induced by neonatal exposure to epidermal growth factor; implication in schizophrenia2012

    • Author(s)
      Nawa H
    • Organizer
      Asian-Pacific Society for Neurochemistry
    • Place of Presentation
      Kobe
    • Related Report
      2012 Annual Research Report
  • [Presentation] Pallidal hyoerdopaminergic states and PPI deficitsinduced byperipheral challenge ofepidermal growth factor to rat neonates2011

    • Author(s)
      Sotoyama H, Zheng Y, Mizuno M,AizawaY, Abe Y, Ishizuka R, Wang R,Iwakura Y, Nawa H
    • Organizer
      The 41st Annual Meeting of Society for thNeuroscience
    • Place of Presentation
      Washington DC, USA.
    • Related Report
      2012 Final Research Report
  • [Presentation] 神経細胞ではAMPKが成長因子によるmTORCシグナル活性化と蛋白合成促進をドミナントに制御する2010

    • Author(s)
      武井延之、石塚佑太、那波宏之
    • Organizer
      第33回日本分子神経生物学会・第83回日本生化学会大会・合同大会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Presentation] Neurotrophic contributionofEGF and neuregulin-1to Parkinson'sdisease and schizophrenia2010

    • Author(s)
      Nawa H
    • Organizer
      Japan-KoreaJoint Conference on Brain Aging and Neurodegeneration
    • Place of Presentation
      Nagasaki JAPAN
    • Related Report
      2012 Final Research Report
  • [Presentation] 那波宏之:ニューレグリン1亜型の示すErbB受容体親和性差とシグナル変化2010

    • Author(s)
      王再、岩倉百合子、武井延之、石塚佑太、鄭英君、加藤泰介、東山繁樹
    • Organizer
      第53回日本神経化学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Book] Methods in Molecular Biology Volume 8292012

    • Author(s)
      Nawa H, Yamada K
    • Publisher
      Hum ana Press, Clifton, New Jersey
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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