Ethylene thiourea exposure induces neurobehavioral toxicity in zebrafish by disrupting axon growth and neuromuscular junctions
Copyright © 2022. Published by Elsevier B.V..
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 62.5 µg/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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:137 |
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| Enthalten in: |
Journal of environmental sciences (China) - 137(2023) vom: 18. März, Seite 108-119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jingming [VerfasserIn] |
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| Links: |
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| Themen: |
24FOJ4N18S |
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| Anmerkungen: |
Date Completed 20.11.2023 Date Revised 20.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jes.2022.11.012 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364715294 |
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| 520 | |a Copyright © 2022. Published by Elsevier B.V. | ||
| 520 | |a 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 62.5 µg/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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Behavior | |
| 650 | 4 | |a Danio rerio | |
| 650 | 4 | |a Ethylene thiourea (ETU) | |
| 650 | 4 | |a MAPK signaling pathway | |
| 650 | 4 | |a Neuromuscular junction | |
| 650 | 4 | |a Piccolo and bassoon | |
| 650 | 7 | |a Ethylenethiourea |2 NLM | |
| 650 | 7 | |a 24FOJ4N18S |2 NLM | |
| 650 | 7 | |a Fungicides, Industrial |2 NLM | |
| 700 | 1 | |a Yu, Zhiquan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yongfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuanyao |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Zong, Yanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Qiyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Lianqi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Huiping |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chunyan |e verfasserin |4 aut | |
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