Abstract：
Tetrabromobisphenol-A-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), a novel additive brominated flame retardant, is being developed for use in polyolefin and copolymers. Despite its emerging application, the neurotoxicity and mechanisms of action of TBBPA-BDBPE remain unexplored. Caenorhabditis elegans was utilized as the model organism to study the neurotoxic effects of TBBPA-BDBPE across environmental concentrations ranging from 0 to 100 μg/L. This investigation focused on various toxicological endpoints such as locomotive behavior, neuronal injury, neurotransmitter transmission, and the regulation of nervous system-related gene expression. Acute exposure to TBBPA-BDBPE at concentrations of 10-100 μg/L significantly impaired nematode movement, indicating potential neurotoxicity. In transgenic nematodes, this exposure also caused damage to γ-aminobutyric acid (GABAergic) and serotonergic neurons, along with notable changes in the levels of GABAergic and serotonergic neurotransmitters. Further molecular studies indicated alterations in neurotransmission-related genes (cat-4, mod-1, unc-25, and unc-47). Molecular docking analysis confirmed the binding affinity of TBBPA-BDBPE to key neurotransmission proteins-CAT-4, MOD-1, UNC-25, and UNC-47. These findings demonstrate that TBBPA-BDBPE exerts neurotoxic effects by impacting GABAergic and serotonergic neurotransmission in nematodes. This study provides new insights into the potential environmental risks of TBBPA-BDBPE.
摘要：
四溴双酚-A-双(2,3-二溴丙基醚)(TBBPA-BDBPE),一种新型添加剂溴化阻燃剂，正在开发用于聚烯烃和共聚物。尽管它的新兴应用，TBBPA-BDBPE的神经毒性和作用机制仍未被研究。利用秀丽隐杆线虫作为模型生物，研究TBBPA-BDBPE在0至100μg/L的环境浓度范围内的神经毒性作用。这项调查集中在各种毒理学终点，如机车行为，神经元损伤，神经递质传递,以及神经系统相关基因表达的调控。急性暴露于浓度为10-100μg/L的TBBPA-BDBPE显着损害了线虫的运动，提示潜在的神经毒性。在转基因线虫中，这种暴露也对γ-氨基丁酸（GABA能）和5-羟色胺能神经元造成损害，随着GABA能和血清素能神经递质水平的显着变化。进一步的分子研究表明神经传递相关基因（cat-4，mod-1，unc-25和unc-47）发生了变化。分子对接分析证实了TBBPA-BDBPE对关键神经传递蛋白-CAT-4、MOD-1、UNC-25和UNC-47的结合亲和力。这些发现表明TBBPA-BDBPE通过影响线虫中的GABA能和5-羟色胺能神经传递而发挥神经毒性作用。这项研究为TBBPA-BDBPE的潜在环境风险提供了新的见解。
