Development of a novel risk assessment method to detect 'disturbance of stress response systems' by environmental chemicals
Project/Area Number |
19K19406
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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Research Institution | University of Toyama |
Principal Investigator |
Tetsushi Hirano 富山大学, 学術研究部薬学・和漢系, 助教 (70804590)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | ストレス応答系 / 化学物質 / AOP / リスク評価 / ストレス応答 / 農薬 / 雌雄差 / バイオマーカー / ネオニコチノイド / 神経毒性 / 環境化学物質 / リスク評価法 |
Outline of Research at the Start |
近年急増しているうつ病や不安障害等のストレス関連精神疾患の原因として,遺伝要因のみならず化学物質等の環境要因が指摘され,発症に関わるメカニズムとして「ストレス応答系のかく乱」が注目されている.しかし,げっ歯類の脳組織変性や肉眼観察を主とする現行の神経毒性試験では,環境化学物質が「ストレス応答系」に及ぼす影響を検出することは不可能である. 本研究では,近代特有の環境要因である環境化学物質が引き起こす「ストレス応答系のかく乱」に関するメカニズムを解明し、新規バイオマーカーおよびリスク評価法を開発することを目的とする.
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Outline of Final Research Achievements |
In this study, we focused on chemical-induced “disturbance of the stress response system”, and through mechanistic analysis using animal models, we were able to elucidate some aspects of a new adverse effect pathway (AOP), with behavioural abnormalities and changes in neural activity as key events during exposure to neonicotinoid pesticides. . Furthermore, omics analysis revealed a set of genes related to neurotransmitter signalling and calcium signalling as candidate biomarkers. In addition, a novel risk assessment system that can efficiently detect synergistic effects of chemicals on neurotoxicity was established using a cellular model, using changes in the activity of proteolytic systems as an indicator.
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Academic Significance and Societal Importance of the Research Achievements |
従来の中枢神経系における化学物質の毒性評価はげっ歯類の脳組織変性や運動失調等を指標としているため、高次脳機能に及ぼす影響に対する検出感度、スループット、再現性の低さが問題点として指摘されている。そのため、「化学物質の曝露が高次脳機能に対して影響を及ぼすのか否か」を検出可能な新規リスク評価法の開発が切望されている。本研究により明らかになったAOPやリスク評価系は、今後、中枢神経系に対する化学物質のリスク評価の高度化を通じて、動物実験の削減や環境負荷の低減に貢献することで持続可能な開発目標(SDGs2, 12, 15等)の達成に寄与することが期待できる。
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Report
(5 results)
Research Products
(57 results)
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[Journal Article] The effects of fipronil on emotional and cognitive behaviors in mammals2021
Author(s)
Suzuki Tomohiro、Hirai Anri、Khidkhan Kraisiri、Nimako Collins、Ichise Takahiro、Takeda Kazuki、Mizukawa Hazuki、Nakayama Shouta M.M.、Nomiyama Kei、Hoshi Nobuhiko、Maeda Mizuki、Hirano Tetsushi、Sasaoka Kazuyoshi、Sasaki Noboru、Takiguchi Mitsuyoshi、Ishizuka Mayumi、Ikenaka Yoshinori
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Journal Title
Pesticide Biochemistry and Physiology
Volume: 3
Pages: 104847-104847
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Fetal and lactational exposure to the no observed adverse effect level (NOAEL) dose of the neonicotinoid pesticide clothianidin inhibits neurogenesis and induces different behavioral abnormalities at the developmental stages in the next generation of male mice2021
Author(s)
Mizuki MAEDA , Sayaka KITA UCHI , Tetsushi HIRANO , Yoshinori IKENAKA, Misaki NISHI , Asuka SHODA , Midori MURATA , Youhei MANTANI , Yoshiaki TABUCHI , Toshifumi YOKOYAMA, Nobuhiko HOSHI
Organizer
4th International Chemical Hazard Symposium
Related Report
Int'l Joint Research
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[Presentation] Transgenerational inheritance effects and the adverse outcome pathway (AOP) of the exposure to the no observed adverse effect level (NOAEL) dose of the neonicotinoid clothianidin in the reproductive organs of female mice2021
Author(s)
Sayak a KITAUCHI , Mizuki MAEDA , Tetsushi HIRANO , Yoshinori IKENAKA , Misaki NISHI , Asuka SHODA , Midori MURATA , Youhei MANTANI , Toshifumi YOKOYAMA, Yoshiaki TABUCHI, Nobuhiko HOSHI
Organizer
4th International Chemical Hazard Symposium
Related Report
Int'l Joint Research
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