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Evaluation of DOHaD hypothesis of chemical-caused dopaminergic disorder

Research Project

Project/Area Number 17K09180
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hygiene and public health
Research InstitutionNational Institute for Environmental Studies

Principal Investigator

Ishido Masami  国立研究開発法人国立環境研究所, 環境リスク・健康領域, シニア研究員 (60211728)

Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords環境化学物質 / DOHaD / 発達障害 / 神経変性疾患 / ドーパミン神経系 / 多動性障害 / DOHaD仮説 / ADHD / エピジェネティク / 遺伝継承毒性 / ADHDモデル / CNV / パーキンソン病 / ロテノン / ドーパミン神経変性 / サイトカイン / MHC / ドーパミン神経疾患 / 化学物質 / ドーパミン神経変性疾患
Outline of Final Research Achievements

Through detailed reconstructions of neonatal and medical histories of birth cohorts in UK, Dr. David Barker proposed the concept that parameters of fetal, infant, and childhood growth may be predictors of disease in later life. In the case of dopaminergic deficit in the development, one could assume that it might result in Parkinson’s disease in the adulthood since the etiology of the disease is the selective loss of dopaminergic neurons.
Rotenone causes two behavioral phenotypes, hyperactivity or hypoactivity. They were created by different timing of chemical exposure, suggesting that there would be a temporal turning point of two behavioral phenotypes. Therefore, we examine a turning point of these behavioral phenotypes by measuring the spontaneous motor activity. We estimate the turning point would be around between three weeks and four weeks of age in the rat dopaminergic neurodegeneration. Gene set enrichment analysis extracts a cytokine network in both rat models.

Academic Significance and Societal Importance of the Research Achievements

Barker博士のDOHaD仮説によれば成人期の疾患の原因は幼少期にあるとする。本研究では当該仮説を環境化学物質ロテノンによるドーパミン神経系疾患について検討した。具体的には新生期ラットのロテノン曝露による多動性障害が老齢期のパーキンソン病の症状を呈するかを調べた。その結果、ロテノンの曝露時期によってその行動特性が変化することが明らかになった。生後5日での曝露により多動性障害が著しく、3~4週齢での曝露によりパーキンソン病の症状を呈することが明らかになった。
こうしたことは環境化学物質の健康リスク評価において曝露時期の要因も考慮しなければならないことを示している。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2023 2022 2021 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Chemical nature of attention deficit hyperactivity disorder (ADHD) - related chemical subfamily2023

    • Author(s)
      Masami Ishido
    • Journal Title

      Chemosphere

      Volume: 313 Pages: 137495-137495

    • DOI

      10.1016/j.chemosphere.2022.137495

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] De novo transgenerational inheritance of male rat hyperactivity by rotenone2022

    • Author(s)
      Masami Ishido
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 9 Pages: 111-1115

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electromagnetic fields (EMF) facilitate cell migration and BrdU incorporation during an EMF-sensitive phase in a rat neurosphere assay in vitro.2020

    • Author(s)
      Masami Ishido
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 7 Pages: 253-257

    • NAID

      130007928571

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A carrier protein is essential for action of silver nanoparticles in an animal experiment2019

    • Author(s)
      Masami Ishido
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 6 Pages: 277-279

    • NAID

      130007731820

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The temporal turning window for rat behavioral phenotypes by rotenone2018

    • Author(s)
      M. Ishido
    • Journal Title

      Fund. Toxicol. Sci.

      Volume: 5 Pages: 195-202

    • NAID

      130007554207

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] An Overview of Development of Quantitative Neurotoxicity Testing In vitro2018

    • Author(s)
      M. Ishido
    • Journal Title

      J. Applied Life Sci. Intl.

      Volume: 19 Pages: 2394-1103

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 超低周波電磁界の神経幹細胞に及ぼす影響評価に関する研究2018

    • Author(s)
      石堂正美
    • Journal Title

      磁気と健康

      Volume: 30 Pages: 20-25

    • Related Report
      2018 Research-status Report
  • [Journal Article] Neonatal rotenone lesions cause onset of hyperactivity during juvenile and adulthood in the rat2017

    • Author(s)
      Ishido Masami、Suzuki Junko、Masuo Yoshinori
    • Journal Title

      Toxicology Letters

      Volume: 266 Pages: 42-48

    • DOI

      10.1016/j.toxlet.2016.12.008

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] エネルギー毒性2021

    • Author(s)
      石堂正美
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] ADHD関連化学物質の生化学的基盤2021

    • Author(s)
      石堂正美
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] DNA methylation profiles in the striatum of hyperactive rats.2020

    • Author(s)
      Masami Ishido
    • Organizer
      日本神経科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] CNV in silver nanoparticle-primed hyperactive rats2019

    • Author(s)
      Masami Ishido
    • Organizer
      EuroTox2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transgeneration of environmental chemicals-primed rat hyperactivity2019

    • Author(s)
      Masami Ishido
    • Organizer
      次世代脳プロジェクトシンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 環境化学物質によるラット多動性障害の病態解析2019

    • Author(s)
      石堂正美
    • Organizer
      先端モデル動物支援プラットフォーム
    • Related Report
      2018 Research-status Report
  • [Presentation] De novo inheritance of environmental chemicals-primed rat hyperactivity2018

    • Author(s)
      M. Ishido
    • Organizer
      第41回日本神経科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Transgeneration of environmental chemicals-primed rat hyperactivity2018

    • Author(s)
      M. Ishido
    • Organizer
      第9回アジア・オセアニア生理学会連合大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Transgeneration of environmental chemicals-primed rat hyperactivity2018

    • Author(s)
      M. Ishido
    • Organizer
      次世代脳プロジェクトシンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Inheritance of environmental chemicals-primed rat hyperactivity2018

    • Author(s)
      M. Ishido
    • Organizer
      第91回日本生化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] A temporal turning point of two behavioral phenotypes2017

    • Author(s)
      石堂正美
    • Organizer
      日本神経科学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2024-01-30  

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