Polystyrene nanoplastics penetrate across the blood-brain barrier and induce activation of microglia in the brain of mice

Abstract

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.

Keywords: Brain-blood barrier; Microglia; Microplastics; Necroptosis; Neurotoxicity.