School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430072, 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.
J Environ Sci (China). 2023 Oct;132:134-144. doi: 10.1016/j.jes.2022.07.012. Epub 2022 Jul 22.
Methylparaben (MeP) is an emerging aquatic pollutant that is found to impact neural functions. However, it still lacks a comprehensive understanding about its neurotoxicology. The present study exposed adult zebrafish to environmentally realistic concentrations (0, 1, 3, and 10 µg/L) of MeP for 28 days, with objectives to elucidate the neurotoxic effects and mechanisms. Proteomic profiling found that MeP pollutant induced distinct mechanism of neurotoxicity as a function of sex. MeP pollutant appeared to preferentially target the neurotransmission cascade via synapse junctions. In male brain, glutamatergic neural signaling was enhanced by 10 µg/L of MeP in characteristics of higher glutamate neurotransmitter content (by 61.9%) and up-regulated glutamate receptor expression by 2.6-fold relative to the control. In MeP-exposed female brain, biomarker proteins of synapse formation and regeneration had significantly lower abundance, accounting for the blockage of synaptic neurotransmission. Furthermore, under the stress of MeP pollutant, both male and female zebrafish initiated a negative feedback mechanism along stress neuroendocrine axis by down-regulating the transcriptions of corticotropin-releasing hormone and its binding protein, which subsequently decreased blood cortisol concentrations. MeP subchronic exposure also disturbed innate immune function. In particular, significant increases in lipopolysaccharide (LPS) content by 15.6% were caused by MeP exposure in male brain, thereby inducing the synthesis of pro-inflammatory cytokines. In contrast, female brain was able to adaptively up-regulate the protein expression of blood brain barrier to inhibit the infiltration of LPS endotoxin into brain. Overall, the present findings pinpoint the potent neurotoxicity of MeP pollutant even at environmentally realistic concentrations.
对羟基苯甲酸甲酯（MeP）是一种新兴的水生污染物，已被发现会影响神经功能。然而，其神经毒理学仍缺乏全面的认识。本研究将成年斑马鱼暴露于环境现实浓度（0、1、3 和 10μg/L）的 MeP 中 28 天，旨在阐明其神经毒性作用和机制。蛋白质组学分析发现，MeP 污染物会根据性别产生不同的神经毒性作用机制。MeP 污染物似乎优先通过突触连接靶向神经递质传递级联。在雄性大脑中，10μg/L 的 MeP 增强了谷氨酸能神经信号，表现为谷氨酸神经递质含量（增加 61.9%）更高，谷氨酸受体表达上调 2.6 倍。在 MeP 暴露的雌性大脑中，突触形成和再生的生物标志物蛋白的丰度显著降低，这解释了突触神经传递的阻断。此外，在 MeP 污染物的应激下，雄性和雌性斑马鱼都通过下调促肾上腺皮质激素释放激素及其结合蛋白的转录来启动应激神经内分泌轴的负反馈机制，从而降低血液皮质醇浓度。MeP 亚慢性暴露还会干扰固有免疫功能。特别是，MeP 暴露使雄性大脑中的脂多糖（LPS）含量增加了 15.6%，从而诱导了促炎细胞因子的合成。相比之下，雌性大脑能够适应性地上调血脑屏障的蛋白表达，以抑制 LPS 内毒素渗透到大脑中。总体而言，本研究结果表明，即使在环境现实浓度下，MeP 污染物也具有很强的神经毒性。
