Shan Shan, Zhang Yifan, Zhao Huiwen, Zeng Tao, Zhao Xiulan
Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Chemosphere. 2022 Jul;298:134261. doi: 10.1016/j.chemosphere.2022.134261. Epub 2022 Mar 14.
Microplastics (MPs) have been well demonstrated as potential threats to the ecosystem, whereas the neurotoxicity of MPs in mammals remains to be elucidated. The current study was designed to investigate whether 50 nm polystyrene nanoplastics (PS-NPs) could pass through the blood-brain barrier (BBB), and to elucidate the underlying mechanisms and the following neurotoxic manifestation. In vivo study showed that PS-NPs (0.5-50 mg/kg. bw PS-NPs for 7 days) significantly induced the increase of permeability of BBB, and dose-dependently accumulated in the brain of mice. In addition, PS-NPs were found to be present in microglia, and induced microglia activation and neuron damage in the mouse brain. In vitro studies using the immortalized human cerebral microvascular endothelial cell (hCMEC/D3), the most commonly used cell model for BBB-related studies, revealed that PS-NPs could be internalized into cells, and caused reactive oxygen species (ROS) production, nuclear factor kappa-B (NF-κB) activation, tumor necrosis factors α (TNF-α) secretion, and necroptosis of hCMEC/D3 cells. Furthermore, PS-NPs exposure led to disturbance of the tight junction (TJ) formed by hCMEC/D3, as demonstrated by the decline of transendothelial electrical resistance (TEER) and decreased expression of occludin. Lastly, PS-NPs exposure resulted in the activation of murine microglia BV2 cells, and the cell medium of PS-NPs-exposed BV2 induced obvious damage to murine neuron HT-22 cells. Collectively, these results suggest that PS-NPs could pass through BBB and induce neurotoxicity in mammals probably by inducing activation of microglia.
微塑料（MPs）已被充分证明是对生态系统的潜在威胁，而微塑料在哺乳动物中的神经毒性仍有待阐明。本研究旨在调查50纳米的聚苯乙烯纳米塑料（PS-NPs）是否能够穿过血脑屏障（BBB），并阐明其潜在机制以及随后的神经毒性表现。体内研究表明，PS-NPs（0.5 - 50毫克/千克体重的PS-NPs，持续7天）显著诱导血脑屏障通透性增加，并在小鼠脑中呈剂量依赖性积累。此外，发现PS-NPs存在于小胶质细胞中，并诱导小鼠脑内小胶质细胞活化和神经元损伤。使用永生化的人脑微血管内皮细胞（hCMEC/D3）进行的体外研究，这是血脑屏障相关研究中最常用的细胞模型，结果显示PS-NPs可被细胞内化，并导致活性氧（ROS）产生、核因子κB（NF-κB）活化、肿瘤坏死因子α（TNF-α）分泌以及hCMEC/D3细胞坏死性凋亡。此外，PS-NPs暴露导致hCMEC/D3形成的紧密连接（TJ）受到干扰，这通过跨内皮电阻（TEER）下降和闭合蛋白表达降低得以证明。最后，PS-NPs暴露导致小鼠小胶质细胞BV2细胞活化，并且暴露于PS-NPs的BV2细胞培养基对小鼠神经元HT-22细胞造成明显损伤。总体而言，这些结果表明PS-NPs可能通过诱导小胶质细胞活化穿过血脑屏障并在哺乳动物中诱导神经毒性。
