State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Neurosurgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
Ecotoxicol Environ Saf. 2022 Aug;241:113754. doi: 10.1016/j.ecoenv.2022.113754. Epub 2022 Jun 13.
Microplastics, a new type of ecological pollutant, have now become a major environmental concern worldwide. Polystyrene microplastics (PS), one of the most abundant form of microplastics, cause deleterious effects across species. Melatonin (MT), which is secreted by pineal gland, exhibits protective role against pollutant-induced damage. However, whether MT could ameliorate PS-induced neurodevelopmental toxicity remain unclear. In our study, zebrafish embryos were treated with PS (0.5, 25 mg/L) in the presence or absence of MT (1 μM) from 4 h post-fertilization (hpf) to 144 hpf. Locomotion behavior, oxidative stress, apoptosis, proliferation and development of caudal primary (Cap) motoneuron axon were analyzed. Gene expression was determined by qRT-PCR or whole-mount in situ hybridization. Results showed that PS exposure significantly reduced swimming speed of zebrafish larvae and induced excessive reactive oxygen species (ROS), apoptosis and aberrant proliferation. In addition, PS treatment markedly shortened the length of Cap motoneuron axons and decreased expression of neurodevelopment related genes. While, MT administration considerably rescued the neurodevelopmental toxicity of PS. Mechanistically, MT activated nrf2 (nuclear factor-E2-related factor 2) - isl2a (ISL LIM homeobox 2a) axis to antagonize the side effects of PS. In all, our findings suggest that PS exposure during early life lead to aberrant neurodevelopment of zebrafish, and MT might be a therapeutic option for protecting such disorder.
微塑料作为一种新型的生态污染物，现已成为全球主要的环境关注点。聚苯乙烯微塑料（PS）是最丰富的微塑料之一，对各种生物都具有有害影响。褪黑素（MT）由松果体分泌，具有抵抗污染物诱导损伤的保护作用。然而，MT 是否能改善 PS 诱导的神经发育毒性尚不清楚。在我们的研究中，从受精后 4 小时（hpf）到 144 hpf，用 PS（0.5、25mg/L）处理斑马鱼胚胎，并在存在或不存在 MT（1μM）的情况下处理。分析了运动行为、氧化应激、细胞凋亡、增殖和尾初级（Cap）运动神经元轴突的发育。通过 qRT-PCR 或全胚胎原位杂交测定基因表达。结果表明，PS 暴露显著降低了斑马鱼幼虫的游泳速度，并诱导了过多的活性氧（ROS）、细胞凋亡和异常增殖。此外，PS 处理显著缩短了 Cap 运动神经元轴突的长度，并降低了神经发育相关基因的表达。而 MT 给药则显著减轻了 PS 的神经发育毒性。在机制上，MT 激活了 nrf2（核因子-E2 相关因子 2）-isl2a（ISL LIM 同源框 2a）轴，拮抗 PS 的副作用。总之，我们的研究结果表明，早期生命中 PS 的暴露会导致斑马鱼的神经发育异常，而 MT 可能是预防这种疾病的一种治疗选择。
