State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Ecotoxicol Environ Saf. 2022 Oct 1;244:114044. doi: 10.1016/j.ecoenv.2022.114044. Epub 2022 Aug 30.
Decabromodiphenyl ethane (DBDPE), a widely used novel brominated flame retardant, is gaining concerns due to rapidly increased contents in various environmental and biota samples. In the present study, zebrafish (Danio rerio) embryos were exposed to 2.91, 9.71, 29.14 and 97.12 μg/L of DBDPE until 120 h post-fertilization (hpf) to investigate the potential developmental neurotoxicity and underlying mechanisms. Chemical analysis revealed concentration-dependently increased body burdens of DBDPE in zebrafish larvae, with bioaccumulation factors (BCFs) ranging from 414 to 726. Embryonic exposure to DBDPE caused hyperactivity without affecting the development of secondary motoneuron axons and muscle fibers. However, further results implicated that DBDPE may affect the locomotor regulatory network via different mechanisms at lower and higher concentrations. On the one hand, embryonic exposure to 2.91 μg/L DBDPE transiently promoted spontaneous coiling contractions, but showed no effects on touch-response and swimming activity in zebrafish larvae. The whole-body contents of neurotransmitters were significantly decreased. Significant decreased protein abundances of α1-TUBULIN and SYN2a and molecular docking results pointed out possible interactions of DBDPE with these two proteins. However, these changes may be unconcerned with the transient hyperactivity, and the exact molecular mechanisms need further investigation. On the other hand, 29.14 and 97.12 μg/L DBDPE exposure caused longer-lasting effects in promoting spontaneous coiling contractions, and also touch-response and swimming activity. At the same time, increased ACh contents (without changes of other neurotransmitters) and ChAT activity and inhibited transcription of nAChRs were observed at higher concentrations. Molecular docking indicated direct interaction of DBDPE with ChAT. The results suggested that DBDPE induced hyperactivity at higher concentrations was probably involved with disrupted cholinergic system, with ChAT as a potential target. Given that the body burden of DBDPE in lower concentration group was comparable with those detected in wild fish, the current results may provide useful information for ecological risk assessment.
十溴二苯乙烷（DBDPE）是一种广泛使用的新型溴化阻燃剂，由于其在各种环境和生物群样本中的含量迅速增加而备受关注。本研究中，将斑马鱼（Danio rerio）胚胎暴露于 2.91、9.71、29.14 和 97.12μg/L 的 DBDPE 中，直至受精后 120 小时（hpf），以研究其潜在的发育神经毒性及其作用机制。化学分析显示，斑马鱼幼虫体内 DBDPE 的浓度呈依赖性增加，生物累积因子（BCF）范围为 414 至 726。胚胎暴露于 DBDPE 会导致过度活跃，但不影响次级运动神经元轴突和肌肉纤维的发育。然而，进一步的结果表明，DBDPE 可能通过不同的机制在较低和较高浓度下影响运动调节网络。一方面，胚胎暴露于 2.91μg/L 的 DBDPE 会短暂地促进自发卷曲收缩，但对斑马鱼幼虫的触摸反应和游泳活动没有影响。神经递质的全身含量显著降低。α1-TUBULIN 和 SYN2a 的蛋白丰度显著降低，分子对接结果表明 DBDPE 可能与这两种蛋白相互作用。然而，这些变化可能与短暂的过度活跃无关，确切的分子机制需要进一步研究。另一方面，29.14 和 97.12μg/L 的 DBDPE 暴露会导致更长时间的自发卷曲收缩、触摸反应和游泳活动的促进作用。同时，在较高浓度下观察到 ACh 含量增加（其他神经递质含量无变化）和 ChAT 活性增强以及 nAChRs 的转录抑制。分子对接表明 DBDPE 与 ChAT 直接相互作用。研究结果表明，在较高浓度下 DBDPE 诱导的过度活跃可能与胆碱能系统的破坏有关，ChAT 可能是一个潜在的靶标。鉴于较低浓度组的 DBDPE 体内负荷与野生鱼类中检测到的负荷相当，因此，当前的结果可能为生态风险评估提供有用的信息。
