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Molecular mechanisms for regression of matured synapses as a neuronal basis for Rett syndrome

Research Project

Project/Area Number 16K19672
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionNational Institute for Physiological Sciences (2017)
Tokyo Women's Medical University (2016)

Principal Investigator

Narushima Madoka  生理学研究所, 基盤神経科学研究領域, 准教授 (30596177)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsシナプス / 発達 / 維持 / mGluR1 / MeCP2 / レット症候群 / 代謝型グルタミン酸受容体 / 外側膝状体 / 退行 / 脳・神経 / 脳神経疾患 / 神経科学 / 生理学
Outline of Final Research Achievements

Rett syndrome is a neurodevelopmental disorder that is induced by a genetic mutation of the Methyl CPG-binding protein 2 (MeCP2) and that is characteristic for regression of once acquired cognitive functions and behaviors. Regression of matured synaptic connectivity has been reported in the afferent synapses of the visual thalamus in MeCP2-knockout (KO) mice but molecular mechanisms underlying regression of synaptic connectivity in relation with MeCP2 was unclear. We reported that KO mice of the metabotropic glutamate receptor subtype 1 (mGluR1) showed similar phenotype as MeCP2-KO mice that exhibited regression of once matured synaptic connectivity in the visual thalamus. mGluR1 expressed in a similar developmental time course with MeCP2 and was necessary and sufficient for maintenance of matured synaptic connectivity in the thalamic afferent synapses. These results strongly suggest that mGluR1 and MeCP2 have strong relationship in the maintenance of matured neuronal circuits.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Comparison of the role of metabotropic glutamate receptor subtype 1 in developmental refinement of neuronal connectivity between the cerebellum and the sensory thalamus2018

    • Author(s)
      Madoka Narushima
    • Journal Title

      Neuroscience Research

      Volume: 129 Pages: 24-31

    • DOI

      10.1016/j.neures.2017.06.004

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Metabotropic Glutamate Receptor Subtype 1 Mediates Experience-Dependent Maintenance of Mature Synaptic Connectivity in the Visual Thalamus2016

    • Author(s)
      Madoka Narushima, Motokazu Uchigashima, Yuki Yagasaki, Takeshi Harada, Yasuyuki Nagumo, Naofumi Uesaka, Kouichi Hashimoto, Atsu Aiba, Masahiko Watanabe, Mariko Miyata and Masanobu Kano
    • Journal Title

      Neuron

      Volume: 91 Issue: 5 Pages: 1097

    • DOI

      10.1016/j.neuron.2016.07.035

    • URL

      https://pure.teikyo.jp/en/publications/bf67227c-49b3-4c38-ae2c-6d003084e0f6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cortical activity regulates refinement of afferent lemniscal synapses in the somatosensory thalamus.2017

    • Author(s)
      Madoka Narushima, Yuichi Takeuchi, Mariko Miyata
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松(静岡県浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] The metabotropic glutamate receptor subtype 1 contributes to developmental refinement of afferent lemniscal synapses in the somatosensory thalamus.2017

    • Author(s)
      鳴島円、竹内雄一、宮田麻理子
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The metabotropic glutamate receptor subtype 1 mediates visual experience-dependent maintenance of synaptic connectivity in the dorsal lateral geniculate nucleus.2017

    • Author(s)
      Madoka Naruhsima, Motokazu Uchigashima, Yuki Yagasaki, Takeshi Harada, Yasuyuki Nagumo, Naofumi Uesaka, Kouichi Hashimoto, Atsu Aiba, Masahiko Watanabe, Mariko Miyata, Masanobu Kano
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The metabotropic glutamate receptor subtype 1 mediates experience-dependent maintenance of mature synaptic connectivity in the dorsal lateral geniculate nucleus2017

    • Author(s)
      Madoka Narushima
    • Organizer
      The 48th NIPS International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Activation of the metabotropic glutamate receptor subtype 1 is necessary for visual experience-dependent maintenance of synaptic connectivity in the dorsal lateral geniculate nucleus.2017

    • Author(s)
      鳴島 円
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The metabotropic glutamate receptor subtype 1 contributes to developmental refinement of afferent lemniscal synapses in the somatosensory thalamus.2016

    • Author(s)
      Madoka Narushima, Yuichi Takeuchi, Mariko Miyata
    • Organizer
      第39回日本神経科学学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Remarks] 成熟した神経回路を維持する仕組みを解明 ~自閉症の病態解明に期待~

    • URL

      http://www.twmu.ac.jp/univ/news/index.php?kbn=1&ym=201608

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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