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Ethylene thiourea exposure induces neurobehavioral toxicity in zebrafish by disrupting axon growth and neuromuscular junctions

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Journal of Environmental Sciences 2024年第3期137卷 108-119页

作者： Jingming Wang Zhiquan Yu Yongfeng Wang Yuanyao Chen Lin Xiao Yanjun Zong Qiyuan Feng Lianqi Peng Huiping Zhang Chunyan Liu Institute of Reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Ethylene thiourea(ETU)converted from ethylene bisdithiocarbamate(EBDC)fungicides has aroused great concern because of its prevalence and harmful effects.Although ETU-induced neurotoxicity has been reported,the potential mechanisms remain unclear.This study provided insights into its neurotoxic effects at environmentally relevant concentrations in zebrafish.Our findings showed that embryonic exposure to ETU decreased the hatch rate and delayed somite development.Furthermore,ETU treatment significantly reduced the dark velocity in the locomotion assay.The upregulated tendency of the mitogen-activated protein kinases(MAPK)pathway(mknk1,atf4,mapkapk3)screened by transcriptome analysis implied motor neuron degeneration,which was validated by subsequent morphological observation,as axon length and branches were truncated in the 62.5μg/L ETU group.However,although the rescue experiment with a p38 MAPK inhibitor(SB203580)successfully ameliorated axon degeneration,it failed to reverse the locomotion behaviors.Further exploration of transcriptome data revealed the varied expression of presynaptic scaffold protein-related genes(pcloa,pclob,bsna),whose downregulation might impair the neuromuscular junction(NMJ).Therefore,we reasonably suspected that ETU-induced neurobehavioral deficits might result from the combined effects of the MAPK pathway and presynaptic proteins.Considering this,we highlighted the necessity to take precautions and early interventions for susceptible ETU-exposed populations.

关键词： Ethylene thiourea(ETU) Behavior Neuromuscular junction MAPK signaling pathway piccolo and bassoon Danio rerio

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