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The RNA-based mechanism underlying pathophysiology in the neurodevelopmental disorders

Research Project

Project/Area Number 15K14355
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokai University

Principal Investigator

IIJIMA Takatoshi  東海大学, 創造科学技術研究機構, 准教授 (90383702)

Research Collaborator SCHEIFFELE Peter  Universität Basel, Dept. of Zellbiologie, Biozentrum, Professor
Project Period (FY) 2015-04-01 – 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords自閉症スペクトラム障害 / バルプロ酸 / 抑制性神経細胞 / シナプス / RNA制御 / 発達障害 / 自閉症 / 精神疾患
Outline of Final Research Achievements

Autism spectrum disorders (ASDs) are a neurodevelopmental disorders characterized by impairments in social interactions and stereotyped behaviors. Valproic acid (VPA) is frequently used to treat epilepsy and bipolar disorders, but increases the risk of the unborn child to develop an ASD during pregnancy. Therefore, VPA-exposed rodent models may allow for identification of synaptic pathophysiology underlying ASD risk. Here, we systematically probed alterations in synaptic proteins that might contribute to autism-related behavior in the offspring of in utero VPA-exposed mice. Moreover, we tested whether direct VPA exposure of cultured neurons may recapitulate the molecular alterations seen in vivo. VPA-exposed neurons in culture exhibit a significant decrease in the number of GABAergic synapses. This shift in excitatory/inhibitory balance results in increased spontaneous activity. Therefore, our study highlights a mechanism underlying the synaptic pathophysiology in this ASD model.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (8 results)

  • [Journal Article] Neuroligin-induced presynaptic differentiation through SLM2-mediated splicing modifications of Neurexin in cerebellar cultures.2017

    • Author(s)
      Yuji Sato, Satoko Suzuki, Yoko Iijima, and Takatoshi Iijima.
    • Journal Title

      Biochemical and Biophysical Research Communications.

      Volume: 17 Issue: 2 Pages: 31868-5

    • DOI

      10.1016/j.bbrc.2017.09.097

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons.2017

    • Author(s)
      Suzuki S, Ayukawa N, Okada C, Tanaka M, Takekoshi S, Iijima Y, Iijima T.
    • Journal Title

      Sci Rep

      Volume: 12 Issue: 1 Pages: 11405-11405

    • DOI

      10.1038/s41598-017-11319-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct Defects in Synaptic Differentiation of Neocortical Neurons in Response to Prenatal Valproate Exposure2016

    • Author(s)
      Yoko Iijima, Katharina Behr, Takatoshi Iijima, Barbara Biemanns, Josef Bischofberger and Peter Scheiffele
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 27400-27400

    • DOI

      10.1038/srep27400

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Activity-dependent bidirectional regulation of GAD expression in a homeostatic fashion is mediated by BDNF-dependent and independent pathways.2015

    • Author(s)
      3.Yoko Hanno-Iijima, Masami Tanaka and Takatoshi Iijima
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 8 Pages: e0134296-e0134296

    • DOI

      10.1371/journal.pone.0134296

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Molecular mechanism and function of alternative pre-mRNA splicing on neuronal cell adhesion molecules regulated by STAR family proteins.2017

    • Author(s)
      Takatoshi Iijima
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Molecular mechanism and function of alternative pre-mRNA splicing on neuronal cell adhesion molecules regulated by STAR family proteins.2017

    • Author(s)
      Takatoshi Iijima, Yoko Iijima, Masami Tanaka, Satoko Suzuki, Noriko Ayukawa, Peter Scheiffele.
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Alternative splicing of Neurexin plays a crucial role in Neuroligin-induced presynaptic differentiation on cerebellar GABAergic neurons in vitro.2017

    • Author(s)
      Yuji Sato, Satoko Suzuki, Yoko Iijima and Takatoshi Iijima.
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Molecular mechanism of alternative pre-mRNA splicing on neuronal cell adhesion molecules regulated by STAR family proteins.2017

    • Author(s)
      Yoko Iijima, Masami Tanaka, Satoko Suzuki, Noriko Ayukawa, Peter Scheiffele and Takatoshi Iijima.
    • Organizer
      第40回日本神経科学学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Alternative splicing of Neurexin plays a crucial role in Neuroligin-induced presynaptic differentiation on cerebellar GABAergic neurons in vitro.2017

    • Author(s)
      Yuji Sato, Satoko Suzuki, Yoko Iijima and Takatoshi Iijima.
    • Organizer
      第40回日本神経科学学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Distinct Defects in Synaptic Differentiation of Neocortical Neurons in Response to Prenatal Valproate Exposure.2016

    • Author(s)
      Yoko Iijima, Katharina Behr, Barbara Biemanns, Josef Bischofberger and Peter Scheiffele, Takatoshi Iijima
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市 パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Distinct Defects in Synaptic Differentiation of Neocortical Neurons in Response to Prenatal Valproate Exposure.2016

    • Author(s)
      Yoko Iijima, Katharina Behr, Barbara Biemanns, Josef Bischofberger and Peter Scheiffele, Takatoshi Iijima
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      神奈川県横浜市 パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] 神経系におけるスプライス多様性の破綻と精神発達疾患2016

    • Author(s)
      飯島崇利
    • Organizer
      第38回日本神経化学会
    • Place of Presentation
      福岡県福岡市 福岡国際会議場
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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