Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells
Roxithromycin (ROX), a commonly used macrolide antibiotic, is extensively employed in human medicine and livestock industries. Due to its structural stability and resistance to biological degradation, ROX persists as a resilient environmental contaminant, detectable in aquatic ecosystems and food pr...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324004032 |
| _version_ | 1797203098673872896 |
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| author | Wenjie Xie Juntao Chen Xiaoqian Cao Jiannan Zhang Juanjuan Luo Yajun Wang |
| author_facet | Wenjie Xie Juntao Chen Xiaoqian Cao Jiannan Zhang Juanjuan Luo Yajun Wang |
| author_sort | Wenjie Xie |
| collection | DOAJ |
| description | Roxithromycin (ROX), a commonly used macrolide antibiotic, is extensively employed in human medicine and livestock industries. Due to its structural stability and resistance to biological degradation, ROX persists as a resilient environmental contaminant, detectable in aquatic ecosystems and food products. However, our understanding of the potential health risks to humans from continuous ROX exposure remains limited. In this study, we used the zebrafish as a vertebrate model to explore the potential developmental toxicity of early ROX exposure, particularly focusing on its effects on locomotor functionality and CaP motoneuron development. Early exposure to ROX induces marked developmental toxicity in zebrafish embryos, significantly reducing hatching rates (n=100), body lengths (n=100), and increased malformation rates (n=100). The zebrafish embryos treated with a corresponding volume of DMSO (0.1%, v/v) served as vehicle controls (veh). Moreover, ROX exposure adversely affected the locomotive capacity of zebrafish embryos, and observations in transgenic zebrafish Tg(hb9:eGFP) revealed axonal loss in motor neurons, evident through reduced or irregular axonal lengths (n=80). Concurrently, abnormal apoptosis in ROX-exposed zebrafish embryos intensified alongside the upregulation of apoptosis-related genes (bax, bcl2, caspase-3a). Single-cell sequencing further disclosed substantial effects of ROX on genes involved in the differentiation of motor neuron progenitor cells (ngn1, olig2), axon development (cd82a, mbpa, plp1b, sema5a), and neuroimmunity (aplnrb, aplnra) in zebrafish larvae (n=30). Furthermore, the CaP motor neuron defects and behavioral deficits induced by ROX can be rescued by administering ngn1 agonist (n=80). In summary, ROX exposure leads to early-life abnormalities in zebrafish motor neurons and locomotor behavior by hindering the differentiation of motor neuron progenitor cells and inducing abnormal apoptosis. |
| first_indexed | 2024-04-24T08:13:56Z |
| format | Article |
| id | doaj.art-67e38a42def94b59a0b1f1d23f6a051d |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-24T08:13:56Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-67e38a42def94b59a0b1f1d23f6a051d2024-04-17T04:48:28ZengElsevierEcotoxicology and Environmental Safety0147-65132024-05-01276116327Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cellsWenjie Xie0Juntao Chen1Xiaoqian Cao2Jiannan Zhang3Juanjuan Luo4Yajun Wang5Key Laboratory of Bioresources and Eco-environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, China; Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou, ChinaKey Laboratory of Bioresources and Eco-environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, China; Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou, ChinaKey Laboratory of Bioresources and Eco-environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, ChinaKey Laboratory of Bioresources and Eco-environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, ChinaEngineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou, China; Correspondence authors.Key Laboratory of Bioresources and Eco-environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, China; Correspondence authors.Roxithromycin (ROX), a commonly used macrolide antibiotic, is extensively employed in human medicine and livestock industries. Due to its structural stability and resistance to biological degradation, ROX persists as a resilient environmental contaminant, detectable in aquatic ecosystems and food products. However, our understanding of the potential health risks to humans from continuous ROX exposure remains limited. In this study, we used the zebrafish as a vertebrate model to explore the potential developmental toxicity of early ROX exposure, particularly focusing on its effects on locomotor functionality and CaP motoneuron development. Early exposure to ROX induces marked developmental toxicity in zebrafish embryos, significantly reducing hatching rates (n=100), body lengths (n=100), and increased malformation rates (n=100). The zebrafish embryos treated with a corresponding volume of DMSO (0.1%, v/v) served as vehicle controls (veh). Moreover, ROX exposure adversely affected the locomotive capacity of zebrafish embryos, and observations in transgenic zebrafish Tg(hb9:eGFP) revealed axonal loss in motor neurons, evident through reduced or irregular axonal lengths (n=80). Concurrently, abnormal apoptosis in ROX-exposed zebrafish embryos intensified alongside the upregulation of apoptosis-related genes (bax, bcl2, caspase-3a). Single-cell sequencing further disclosed substantial effects of ROX on genes involved in the differentiation of motor neuron progenitor cells (ngn1, olig2), axon development (cd82a, mbpa, plp1b, sema5a), and neuroimmunity (aplnrb, aplnra) in zebrafish larvae (n=30). Furthermore, the CaP motor neuron defects and behavioral deficits induced by ROX can be rescued by administering ngn1 agonist (n=80). In summary, ROX exposure leads to early-life abnormalities in zebrafish motor neurons and locomotor behavior by hindering the differentiation of motor neuron progenitor cells and inducing abnormal apoptosis.http://www.sciencedirect.com/science/article/pii/S0147651324004032RoxithromycinLocomotory behaviorMotoneuron developmentZebrafish |
| spellingShingle | Wenjie Xie Juntao Chen Xiaoqian Cao Jiannan Zhang Juanjuan Luo Yajun Wang Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells Ecotoxicology and Environmental Safety Roxithromycin Locomotory behavior Motoneuron development Zebrafish |
| title | Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells |
| title_full | Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells |
| title_fullStr | Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells |
| title_full_unstemmed | Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells |
| title_short | Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells |
| title_sort | roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells |
| topic | Roxithromycin Locomotory behavior Motoneuron development Zebrafish |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324004032 |
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