Mechanisms Underlying the Size-Dependent Neurotoxicity of Polystyrene Nanoplastics in Zebrafish

IF 10.8 1区 环境科学与生态学 Q1 ENGINEERING, ENVIRONMENTAL 环境科学与技术 Pub Date : 2025-01-16 DOI:10.1021/acs.est.4c12148
Chao Wu, Hong-Jie Zhang, Hongxia Ma, Rong Ji, Ke Pan, Tongtao Yue, Ai-Jun Miao
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Abstract

Nanoplastics (NPs) are ubiquitous in the environment, posing significant threats to biological systems, including nervous systems, across various trophic levels. Nevertheless, the molecular mechanisms behind the size-dependent neurotoxicity of NPs remain unclear. Here, we investigated the neurotoxicity of 20 and 100 nm polystyrene NPs (PS-NPs) to zebrafish. Utilizing molecular dynamics simulations and complementary methods, we discovered that PS-NPs initiated neurotoxicity by promoting dimerization of the toll-like receptor 4/myeloid differentiation-2 (TLR4/MD-2) complex. This process involves the binding of PS-NPs to the hydrophobic pocket of MD-2, which induced the flipping of Phe-126 toward the dimer interface and the bending of the C-terminal domain of TLR-4, bringing the two domains into close proximity. Thereafter, the astrocytes and microglia were activated, initiating a cascade of events that include neuroinflammation, central nervous system cell apoptosis, inhibition of motor neuron development, and ultimately alteration of the swimming behavior of zebrafish. Further, 20 nm PS-NPs elicited more severe neurotoxicity than 100 nm PS-NPs, attributed to their higher accumulation in the brain as determined through 14C-labeled PS-NPs and more effective interaction with the TLR4/MD-2 complex. Overall, our study uncovers the mechanisms underlying the size-dependent neurotoxicity of NPs, which merit attention during their risk assessment and regulation.

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聚苯乙烯纳米塑料对斑马鱼的大小依赖性神经毒性机制
纳米塑料(NPs)在环境中无处不在,对不同营养级的生物系统(包括神经系统)构成重大威胁。然而,NPs 尺寸依赖性神经毒性背后的分子机制仍不清楚。在这里,我们研究了 20 纳米和 100 纳米聚苯乙烯 NPs(PS-NPs)对斑马鱼的神经毒性。利用分子动力学模拟和补充方法,我们发现 PS-NPs 通过促进收费样受体 4/髓系分化-2(TLR4/MD-2)复合物的二聚化而引发神经毒性。这一过程涉及 PS-NPs 与 MD-2 的疏水口袋结合,从而诱导 Phe-126 向二聚体界面翻转,并使 TLR-4 的 C 端结构域弯曲,使这两个结构域靠近。此后,星形胶质细胞和小胶质细胞被激活,引发了一连串的事件,包括神经炎症、中枢神经系统细胞凋亡、运动神经元发育受抑制,并最终改变了斑马鱼的游泳行为。此外,20 nm PS-NPs 比 100 nm PS-NPs 引发了更严重的神经毒性,这归因于通过 14C 标记的 PS-NPs 确定了它们在大脑中更高的蓄积量,以及与 TLR4/MD-2 复合物更有效的相互作用。总之,我们的研究揭示了 NPs 尺寸依赖性神经毒性的内在机制,值得在风险评估和监管过程中加以关注。
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来源期刊
环境科学与技术
环境科学与技术 环境科学-工程:环境
CiteScore
17.50
自引率
9.60%
发文量
12359
审稿时长
2.8 months
期刊介绍: Environmental Science & Technology (ES&T) is a co-sponsored academic and technical magazine by the Hubei Provincial Environmental Protection Bureau and the Hubei Provincial Academy of Environmental Sciences. Environmental Science & Technology (ES&T) holds the status of Chinese core journals, scientific papers source journals of China, Chinese Science Citation Database source journals, and Chinese Academic Journal Comprehensive Evaluation Database source journals. This publication focuses on the academic field of environmental protection, featuring articles related to environmental protection and technical advancements.
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