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在环境相关浓度下发育性暴露于铅会损害斑马鱼幼虫的神经行为和 NMDAR 依赖性 BDNF 信号传导。

Developmental exposure to lead at environmentally relevant concentrations impaired neurobehavior and NMDAR-dependent BDNF signaling in zebrafish larvae.

机构信息

WEEE Research Centre of Shanghai Polytechnic University, Shanghai Collaborative Innovation Centre for WEEE Recycling, Shanghai, 201209, China; Research Center of Resource Recycling Science and Engineering, Shanghai Polytechnic University, Shanghai, 201209, China.

Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.

出版信息

Environ Pollut. 2020 Feb;257:113627. doi: 10.1016/j.envpol.2019.113627. Epub 2019 Nov 21.

Abstract

Lead (Pb) is one of the predominant heavy metals in e-waste recycling arears and recognized as a notorious environmental neurotoxic substance. However, whether Pb at environmentally relevant concentrations could cause neurobehavioral alteration and even what kind of signaling pathway Pb exposure would disrupt in zebrafish were not fully uncovered. In the present study, 6 h postfertilization (hpf) zebrafish embryos were exposed to Pb at the concentrations of 0, 5, 10, and 20 μg/L until 144 hpf. Then the neurobehavioral indicators including locomotor, turnings and social behaviors, and the expressions of selected genes concerning brain-derived neurotrophic factor (BDNF) signaling were investigated. The results showed that significant changes were obtained under 20 μg/L Pb exposure. The hypoactivity of zebrafish larvae in locomotor and turning behaviors was induced during the dark period, while hyperactivity was observed in a two-fish social assay during the light period. The significantly downregulation of genes encoding BDNF, its receptor TrkB, and N-methyl-D-aspartate glutamate receptor (NMDAR) suggested the involvement of NMDAR-dependent BDNF signaling pathway. Overall, our study demonstrated that developmental exposure to Pb at environmentally relevant concentrations caused obvious neurobehavioral impairment of zebrafish larvae by disrupting the NMDAR-dependent BDNF signaling, which could exert profound ecological consequences in the real environment.

摘要

铅(Pb)是电子废物回收区主要的重金属之一,被认为是一种臭名昭著的环境神经毒性物质。然而,环境相关浓度的 Pb 是否会导致神经行为改变,甚至 Pb 暴露会破坏斑马鱼中的哪种信号通路,这些问题尚未完全阐明。在本研究中,受精后 6 小时(hpf)的斑马鱼胚胎在 0、5、10 和 20μg/L 的 Pb 浓度下暴露至 144 hpf。然后,研究了与脑源性神经营养因子(BDNF)信号有关的神经行为指标,包括运动、转弯和社会行为,以及选定基因的表达。结果表明,在 20μg/L Pb 暴露下,出现了显著的变化。在黑暗期,斑马鱼幼虫的运动和转弯行为出现活动减少,而在光照期的双鱼社会试验中,出现了过度活动。编码 BDNF、其受体 TrkB 和 N-甲基-D-天冬氨酸谷氨酸受体(NMDAR)的基因表达显著下调,表明 NMDAR 依赖性 BDNF 信号通路的参与。总的来说,我们的研究表明,在环境相关浓度下,发育暴露于 Pb 会通过破坏 NMDAR 依赖性 BDNF 信号通路,导致斑马鱼幼虫明显的神经行为损伤,这可能会对真实环境产生深远的生态后果。

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