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Pathophysiological alterations of intrinsic properties and neural activity in the midbrain dopaminergic neurons mediated by neurotrophic factors

Research Project

Project/Area Number 23500464
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionNiigata University

Principal Investigator

NAMBA Hisaaki  新潟大学, 脳研究所, 助教 (90332650)

Co-Investigator(Renkei-kenkyūsha) NAWA Hiroyuki  新潟大学, 脳研究所, 教授 (50183083)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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ドパミン / 神経栄養因子 / ニューレグリン / 上皮成長因子 / スパイク発火特性 / 動物モデル / 統合失調症 / 生理特性
Research Abstract

Neuregulin (NRG) and epidermal growth factor (EGF) have nerurotrophic activities on the midbrain dopaminergic neurons. These factors are implicated with the etiology of neuropsychiatric diseases, such as schizophrenia. NRG/EGF administered rodents during neonatal period exhibit behavioral abnormalities related with schizophrenia. Therefore, these animals are useful models to analyze the neuronal mechanisms underlying the pathophysiology. Slice patch-clamp analyzes of the dopaminergic neurons reveal that NRG or EGF attenuated synaptic inhibition or spike after-hyperpolarization mediated by a certain potassium current, respectively, both of which potentially enhance neural activity. In support of this, in vivo burst firing activity was enhanced under anesthetic condition in NRG or EGF administered animals. Thus, pathophysiological alterations of neuronal properties might participate in abnormal dopaminergic transmission and behavioral traits in the animal models for schizophrenia.

Report

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

    (10 results)

All 2013 2011

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (7 results)

  • [Journal Article] ErbB inhibitors ameliorate behavioral impairments of an animal model for schizophrenia : implication of their dopamine-modulatory actions2013

    • Author(s)
      Mizuno M, Sotoyama H, Namba H, Shibuya M, Eda T, Wang R, Okubo T, Nagata K, Iwakura Y, Nawa H
    • Journal Title

      Transl Psychiatry

      Volume: 3

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [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
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] ErbB inhibitors ameliorate behavioral impairments of an animal model for schizophrenia: implication of their dopamine-modulatory actions.2013

    • Author(s)
      Mizuno M, Sotoyama H, Namba H, Shibuya M, Eda T, Wang R, Okubo T, Nagata K, Iwakura Y, Nawa H.
    • Journal Title

      Transl Psychiatry.

      Volume: 3 Issue: 4 Pages: e252-e252

    • DOI

      10.1038/tp.2013.29

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 2 種の幼若期栄養因子投与マウスの in vivo麻酔下での中脳ドパミン神経活動変化( Abnormal firing activities of the midbrain dopaminergic neurons in the mice treated with EGF and neuregulin-1 as neonate.)2013

    • Author(s)
      難波寿明, 大久保猛司, 那波宏之
    • Organizer
      第36回日本神経科学大会(Neuro2013)
    • Place of Presentation
      京都
    • Year and Date
      2013-06-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 上皮成長因子によって確立された統合失調症動物モデルにおける腹側被蓋野-前頭皮質経路の機能異常(Abnormal ventral tegmental area - medial prefrontal cortex dopaminergic pathway of the schizophrenia animal model established by epidermal growth factor)2013

    • Author(s)
      外山英和, 難波寿明, 那波宏之
    • Organizer
      第36回日本神経科学大会(Neuro2013)
    • Place of Presentation
      京都
    • Year and Date
      2013-06-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Pathophysiological alterations of in vivo activity and intrinsic property of mature dopaminergic neuron in the epidermal growth factor-administered mice as neonate.2013

    • Author(s)
      難波寿明、那波宏之
    • Organizer
      Dopamine2013
    • Place of Presentation
      イタリア(アルゲーロ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2種の幼若期栄養因子投与マウスのin vivo麻酔下での中脳ドパミン神経活動変化 (Abnormal firing activities of the midbrain dopaminergic neurons in the mice treated with EGF and neuregulin-1 as neonate.)2013

    • Author(s)
      難波寿明、大久保猛司、那波宏之
    • Organizer
      第36回日本神経科学大会(Neuro2013)
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 上皮成長因子によって確立された統合失調症動物モデルにおける腹側被蓋野-前頭皮質ドパミン経路の機能異常 (Abnormal ventral tegmental area - medial prefrontal cortex dopaminergic pathway of the schizophrenia animal model established by epidermal growth factor)2013

    • Author(s)
      外山英和 難波寿明 那波宏之
    • Organizer
      第36回日本神経科学大会(Neuro2013)
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 幼若期ニューレグリン投与マウスにおける中脳ドパミン神経の生理特性( Electrophysiological properties of adult midbrain dopaminergic neurons of the mice treated with neuregulin-1 as neonates.)2011

    • Author(s)
      難波寿明, 竹田悠亮, 那波宏之
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 幼若期ニューレグリン投与マウスにおける中脳ドパミン神経の生理特性2011

    • Author(s)
      難波寿明、竹田悠亮、那波宏之
    • Organizer
      第34回日本神経科学学会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report

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

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