6-PPD醌(6-PPDQ),一种新兴的环境污染物,通过臭氧化基于6-PPD转化。然而,对长期低剂量6-PPDQ暴露可能的神经毒性及其潜在机制的系统评估仍然未知.在目前的工作中,添加0.1-10μg/L6-PPDQ治疗秀丽隐杆线虫4.5天,随着运动行为,神经元发育,感官知觉行为,神经递质含量,神经传递相关基因的水平是终点。6-PPDQ暴露在0.1-10μg/L显著降低运动行为,并且在1-10μg/L时降低了线虫的感官知觉行为。此外,以10μg/L的6-PPDQ暴露会引起多巴胺能发育的损伤,谷氨酸能,血清素能,和GABA能神经元。重要的是,慢性6-PPDQ暴露于10μg/L的线虫被证实患有明显减少的多巴胺,血清素,谷氨酸,多巴胺,和GABA含量和改变神经传递相关基因表达。同时,通过分子对接方法进一步显示了6-PPDQ和神经递质合成相关蛋白的潜在结合位点。最后,Pearson相关分析显示运动行为和感觉知觉行为与多巴胺能,血清素能,谷氨酸能,和GABA能神经传递。因此,6-PPDQ暴露干扰神经递质传递,而这种改变的神经递质传递的分子基础与6-PPDQ毒性诱导有关。目前的工作为6-PPDQ的机制及其在环境相关浓度下对生物体的神经毒性提供了新的思路。
6-PPD quinone (6-PPDQ), an emerging environmental pollutant, is converted based on 6-PPD via ozonation. However, a systematic evaluation on possible neurotoxicity of long-term and low-dose 6-PPDQ exposure and the underlying mechanism remain unknown. In the present work, 0.1-10 μg/L 6-PPDQ was added to treat Caenorhabditis elegans for 4.5 days, with locomotion behavior, neuronal development, sensory perception behavior, neurotransmitter content, and levels of
neurotransmission-related genes being the endpoints. 6-PPDQ exposure at 0.1-10 μg/L significantly reduced locomotion behavior, and that at 1-10 μg/L decreased sensory perception behavior in nematodes. Moreover, 6-PPDQ exposure at 10 μg/L notably induced damage to the development of dopaminergic, glutamatergic, serotonergic, and GABAergic neurons. Importantly, nematodes with chronic 6-PPDQ exposure at 10 μg/L were confirmed to suffer obviously decreased dopamine, serotonin, glutamate, dopamine, and GABA contents and altered
neurotransmission-related gene expression. Meanwhile, the potential binding sites of 6-PPDQ and neurotransmitter synthesis-related proteins were further shown by molecular docking method. Lastly, Pearson\'s correlation analysis showed that locomotion behavior and sensory perception behavior were positively correlated with the dopaminergic, serotonergic, glutamatergic, and GABAergic
neurotransmission. Consequently, 6-PPDQ exposure disturbed neurotransmitter transmission, while such changed molecular foundation for neurotransmitter transmission was related to 6-PPDQ toxicity induction. The present work sheds new lights on the mechanisms of 6-PPDQ and its possible neurotoxicity to organisms at environmentally relevant concentrations.