Polystyrene nanoplastics induced learning and memory impairments in mice by damaging the glymphatic system

The excessive usage of nanoplastics (NPs) has posed a serious threat to the ecological environment and human health, which can enter the brain and then result in neurotoxicity. However, research on the neurotoxic effects of NPs based on different exposure routes and modifications of functional groups is lacking. In this study, the neurotoxicity induced by NPs was studied using polystyrene nanoplastics (PS-NPs) of different modifications (PS, PS-COOH, and PS-NH2). It was found that PS-NH2 through intranasal administration (INA) exposure route exhibited the greatest accumulation in the mice brain after exposure for 7 days. After the mice were exposed to PS-NH2 by INA means for 28 days, the exploratory ability and spatial learning ability were obviously damaged in a dose-dependent manner. Further analysis indicated that these damages induced by PS-NH2 were closely related to the decreased ability of glymphatic system to clear β-amyloid (Aβ) and phosphorylated Tau (P-Tau) proteins, which was ascribed to the loss of aquaporin-4 (AQP4) polarization in the astrocytic endfeet. Moreover, the loss of AQP4 polarization might be regulated by the NF-κB pathway. Our current study establishes the connection between the neurotoxicity induced by PS-NPs and the glymphatic system dysfunction for the first time, which will contribute to future research on the neurotoxicity of NPs.