Effects of pesticide exposure on central synapse formation
Project/Area Number |
19K19407
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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 |
Izumi Hironori 富山大学, 医学部, 技術専門職員 (00377342)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 農薬曝露 / 神経シナプス形成 / 発達神経毒性 / 有機リン系農薬 / ピレスロイド系農薬 / 神経毒性 |
Outline of Research at the Start |
農薬曝露による神経系への影響として、高次脳機能障害を伴う発達障害が問題視されている。本研究では、グルホシネート(有機リン系農薬)やデルタメトリン(ピレスロイド系農薬)の曝露による神経シナプス形成への影響評価を通して、神経発達障害の病態発症機構の解明に取り組む。農薬曝露に起因するシナプス病態を明らかにすることで、多様な神経発達障害の治療戦略の基盤構築に大きく貢献できる。
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Outline of Final Research Achievements |
The purpose of this study is to elucidate the pathogenic mechanism underlying neurodevelopmental disorders through evaluation of the effects of pesticide exposure on the synapse formation in central nervous system. Our study showed changes in the amount of presynaptic differentiation in cultured neurons of fetal mice with maternal exposure to organophosphorus pesticide, glufosinate ammonium (GLA) compared to saline-control group. We also identified differentially expressed genes related to nervous system development between GLA-treated and saline-control groups by the transcriptome analysis of primary cultured cortical neurons. On the other hand, through the production and analysis of Ptprd gene mutant mice, we found that this gene contributes to the induction of specific presynaptic differentiation. In addition, we demonstrated that changes in social behavior was induced in mutant mice in which presynaptic competitive interactions are genetically biased.
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Academic Significance and Societal Importance of the Research Achievements |
本研究によって、これまで農薬曝露による中枢神経系への影響では明らかになっていなかった神経シナプスにおける病態を新たな知見として得られたことは学術的に大きな意義がある。本研究の応用により、農薬を含む化学物質が高次脳機能に与える影響を簡便且つ高感度に検出可能なリスク評価法の開発が期待できる。また、シナプス病態から学習・行動異常を引き起こす細胞集団の特徴付けを行うことで、神経発達障害に対する治療戦略の基盤構築に結び付くと考えられる。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities.2021
Author(s)
Yaku K, Palikhe S, Izumi H, Yoshida T, Hikosaka K, Hayat F, Karim M, Iqbal T, Nitta Y, Sato A, Migaud ME, Ishihara K, Mori H, Nakagawa T
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 6767-6767
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Generation and characterization of a Meflin-CreERT2 transgenic line for lineage tracing in white adipose tissue2021
Author(s)
Kuwano Takahide, Izumi Hironori, Aslam Muhammad Rahil, Igarashi Yoshiko, Bilal Muhammad, Nishimura Ayumi, Watanabe Yoshiyuki, Nawaz Allah, Kado Tomonobu, Ikuta Koichi, Yamamoto Seiji, Sasahara Masakiyo, Fujisaka Shiho, Yagi Kunimasa, Mori Hisashi, Tobe Kazuyuki
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Journal Title
PLOS ONE
Volume: 16
Issue: 3
Pages: e0248267-e0248267
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice2021
Author(s)
Yoshida T, Yamagata A, Imai A, Kim J, Izumi H, Nakashima S, Shiroshima T, Maeda A, Iwasawa-Okamoto S, Azechi K, Osaka F, Saitoh T, Maenaka K, Shimada T, Fukata Y, Fukata M, Matsumoto J, Nishijo H, Takao K, Tanaka S, Okabe S, Tabuchi K, Uemura T, Mishina M, Mori H & Fukai S
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Journal Title
Nature Communications
Volume: 12(1)
Issue: 1
Pages: 1848-1848
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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