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Elucidating of pathogenesis of autism by comprehensive and quantitative analysis of synaptic signaling

Research Project

Project/Area Number 16K21046
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Psychiatric science
Neurochemistry/Neuropharmacology
Research InstitutionNiigata University

Principal Investigator

Egawa Jun  新潟大学, 医歯学総合研究科, 特任准教授 (80648527)

Research Collaborator Igarashi Michihiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords自閉スペクトラム症 / NLGN3 / 機能解析 / リン酸化プロテオミクス / シナプス画分 / GAP43 / 機能的リン酸化部位 / 児童思春期精神医学 / 神経生化学
Outline of Final Research Achievements

We selected NLGN3, which are risk genes for autism spectrum disorder (ASD), among genes whose phosphorylation sites are important for neurodevelopment identified by phosphoproteomics of growth cones, and performed functional analysis. The distribution of the phosphorylation site (S745) of NLGN3 was subjected to immunoblotting using synaptosomes, and immunohistological observation using primary culture neurons. These findings suggest that phosphorylation may be functional at both the axonal tip and the synapse.

Academic Significance and Societal Importance of the Research Achievements

ASDの妥当性の高いリスク遺伝子は全エクソーム解析などの網羅的な解析法によって同定された。本研究ではタンパクレベルの網羅的解析であるリン酸化プロテオミクスで同定された神経発達に重要と考えられるリン酸化部位のうちASDのリスク遺伝子に存在するものを選定してそれらの機能についての知見を得ることができた。タンパクレベルの妥当性の高い知見を蓄積することにより、さらに高次レベルの知見を得るための確かな土台となる。このように各レベルで妥当性の高い土台を重ねていくことにより、ASDの病態解明および治療法開発に結び付くと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights.2018

    • Author(s)
      Kushima I, (27名中略), Hashimoto R,(80名中29番目) , et al.
    • Journal Title

      Cell Rep

      Volume: 24(11) Issue: 11 Pages: 2838-2856

    • DOI

      10.1016/j.celrep.2018.08.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rare loss of function mutations in N-methyl-d-aspartate glutamate receptors and their contributions to schizophrenia susceptibility2018

    • Author(s)
      Yu Yanjie、Lin Yingni、Takasaki Yuto、Wang Chenyao、Kimura Hiroki、Xing Jingrui、Ishizuka Kanako、Toyama Miho、Kushima Itaru、Mori Daisuke、Arioka Yuko、Uno Yota、Shiino Tomoko、Nakamura Yukako、Okada Takashi、Morikawa Mako、Ikeda Masashi、Iwata Nakao、Okahisa Yuko、Takaki Manabu、Sakamoto Shinji、et al.
    • Journal Title

      Translational Psychiatry

      Volume: 8 Issue: 1 Pages: 12-20

    • DOI

      10.1038/s41398-017-0061-y

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders2017

    • Author(s)
      Ishizuka K、Fujita Y、Kawabata T、Kimura H、Iwayama Y、Inada T、Okahisa Y、Egawa J、Usami M、Kushima I、Uno Y、Okada T、Ikeda M、Aleksic B、Mori D、Someya To、Yoshikawa T、Iwata N、Nakamura H、Yamashita T、Ozaki N
    • Journal Title

      Translational Psychiatry

      Volume: 7 Issue: 8 Pages: e1184-e1184

    • DOI

      10.1038/tp.2017.173

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rare FBOX18 variations and risk of schizophrenia: whole-exome sequencing in two parent-affected offspring trios followed by resequencing and case-control studies.2017

    • Author(s)
      Hoya S, Watabe Y, Hishimoto A, Nunokawa A, Inoue E, Igeta H, Otsuka I, Shibuya M, Egawa J, Sora I, Someya T
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 印刷中 Issue: 8 Pages: 562-568

    • DOI

      10.1111/pcn.12526

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Rare PDCD11 variations are not associated with risk of schizophrenia in Japan2017

    • Author(s)
      Hoya Satoshi、Watanabe Yuichiro、Hishimoto Akitoyo、Nunokawa Ayako、Kaneko Naoshi、Muratake Tatsuyuki、Shinmyo Naofumi、Otsuka Ikuo、Okuda Shujiro、Inoue Emiko、Igeta Hirofumi、Shibuya Masako、Egawa Jun、Orime Naoki、Sora Ichiro、Someya Toshiyuki
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 71 Issue: 11 Pages: 780-788

    • DOI

      10.1111/pcn.12549

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 自閉症リスク遺伝子Neuroligin3の機能的リン酸化部位の機能解析2019

    • Author(s)
      江川純, 五十嵐道弘, 染矢俊幸
    • Organizer
      第115回日本精神神経学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 拡散テンソル画像を用いた脳機能結合と自閉スペクトラム症との関連解析2019

    • Author(s)
      江川純, 杉本篤言, 吉永清宏, 林剛丞, 染矢俊幸
    • Organizer
      第115回日本精神神経学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Relationship between prefrontal cortex activity during task execution and ADHD symptoms of adult patients, and their changes by atomoxetine.2018

    • Author(s)
      Sugimoto A, Suzuki Y, Yoshinaga K, Orime N, Hayashi T, Egawa J, Ono S, Sugai T, Someya T
    • Organizer
      WFSBP Asia Pacific Regional Congress of Biological Psychiatry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Resequencing of the SETD1A gene in Japanese patients with schizophrenia2018

    • Author(s)
      Hoya S, Igeta H, Watanabe Y, Nunokawa A, Inoue E, Shibuya M, Egawa J, Someya T
    • Organizer
      WFSBP Asia Pacific Regional Congress of Biological Psychiatry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Resequencing and association analysis of CLN8 with autism spectrum disorder in a Japanese population.2016

    • Author(s)
      江川純
    • Organizer
      22nd World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions
    • Place of Presentation
      Calgary CANADA
    • Year and Date
      2016-09-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 自閉スペクトラム症罹患一卵性双生児を含む家系におけるエクソームシークエンスおよびフォローアップ解析.2016

    • Author(s)
      江川純
    • Organizer
      第38回日本生物学的精神医学会・第59回日本神経化学会大会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] Rare missense variations and risk of autism: Whole-exome sequencing in affected sib-pair families.2016

    • Author(s)
      江川純
    • Organizer
      第38回日本生物学的精神医学会・第59回日本神経化学会大会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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