Chao Wu, Hong-Jie Zhang, Hongxia Ma, Rong Ji, Ke Pan, Tongtao Yue, Ai-Jun Miao
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引用次数: 0
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.
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.