Effects of pesticide exposure on central synapse formation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19407
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: University of Toyama
• Principal Investigator: Izumi Hironori 富山大学, 医学部, 技術専門職員 (00377342)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 農薬曝露 / 神経シナプス形成 / 発達神経毒性

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.

Free Research Field

発達神経毒性学、公衆衛生学、神経科学、実験動物学

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。