Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, China; The Center for Disease Control and Prevention, Dalian Jinzhou New District, Dalian, China.
Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, China; Department of Planned Immunization, Liaoning Provincial Center for Disease Control and Prevention, Shenyang, China.
Ecotoxicol Environ Saf. 2024 Apr 1;274:116196. doi: 10.1016/j.ecoenv.2024.116196. Epub 2024 Mar 10.
Deltamethrin (DM) is a highly effective and widely used pyrethroid pesticide. It is an environmental factor affecting public and occupational health and exerts direct toxic effects on the central nervous system. As the major target organs for neurotoxicity of DM, the hippocampus and the cerebellum are critical to the learning and motor function. Pregnant Wistar rats were randomly divided into four groups and gavaged at doses of 0, 1, 4or 10 mg/kg/d DM from gestational day (GD) 0 to postnatal day (PN) 21. The PC12 cells were selected to further verify the regulatory mechanisms of DM on the neurodevelopmental injury. We found that maternal exposure to DM caused learning, memory and motor dysfunction in male offspring. Maternal exposure to DM induced the decrease in the density of hippocampal dendritic spines in male offspring through the reduced expression of M1 mAchRs, which in turn reduced the mediated AKT/mTOR signaling pathway, contributing to the inhibition of dynamic changes of GluA1. Meanwhile, DM exposure inhibited the BDNF/TrkB signaling pathway, thereby reducing phosphorylation of stathmin and impairing cerebellar purkinje cell dendrite growth and development. Taken together, maternal exposure to DM during pregnancy and lactation could impair neurodevelopment of male offspring.
溴氰菊酯（DM）是一种高效且广泛使用的拟除虫菊酯类农药。它是影响公众和职业健康的环境因素，对中枢神经系统具有直接毒性作用。作为 DM 神经毒性的主要靶器官，海马体和小脑对于学习和运动功能至关重要。妊娠 Wistar 大鼠随机分为四组，从妊娠 0 天（GD）到产后 21 天（PN），每天灌胃 0、1、4 或 10mg/kg/d DM。选择 PC12 细胞进一步验证 DM 对神经发育损伤的调节机制。我们发现，母体暴露于 DM 会导致雄性后代出现学习、记忆和运动功能障碍。母体暴露于 DM 通过降低 M1 mAchR 的表达，导致雄性后代海马树突棘密度降低，进而减少 AKT/mTOR 信号通路的介导，导致 GluA1 的动态变化受到抑制。同时，DM 暴露抑制了 BDNF/TrkB 信号通路，从而减少了 stathmin 的磷酸化，损害了小脑浦肯野细胞树突的生长和发育。总之，母体在妊娠和哺乳期暴露于 DM 可能会损害雄性后代的神经发育。
