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

作　　者：Jingming Wang Zhiquan Yu Yongfeng Wang Yuanyao Chen Lin Xiao Yanjun Zong Qiyuan Feng Lianqi Peng Huiping Zhang Chunyan Liu 

机构地区：[1]Institute of Reproductive Health,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Journal of Environmental Sciences》2024年第3期108-119,共12页环境科学学报（英文版）

基　　金：supported by the National Key R&D Program of China (Nos.2018YFC1004300 and 2018YFC1004304)。

摘　　要：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 

分 类 号：X171.5[环境科学与工程—环境科学]