Amine-modified polystyrene particles induce surface chemistry-driven immunotoxicity in microglia: Protective effects of trolox

Microplastics are increasingly prevalent environmental contaminants that pose potential risks to human health, particularly affecting the central nervous system. This study investigated the mechanisms by which surface modification of polystyrene microplastics affects their neurotoxicity in microglial cells. The results indicated that amine-modified polystyrene (PS-NH 2 ) microplastics induce substantially higher cytotoxicity in BV2 microglial cells than that by plain polystyrene or carboxyl-modified polystyrene at the same concentration. PS-NH 2 particles were rapidly internalized by microglia, inducing pronounced inflammatory responses, including elevated expression of proinflammatory cytokines (TNF-α and IL-6) and M1 polarization markers. Furthermore, our findings indicated that PS-NH 2 induced mitochondrial damage accompanied by sustained superoxide accumulation, which led to cellular oxidative stress associated with nitric oxide synthesis and apoptosis. Mitochondrial superoxide production, particularly via complex II and III inhibition, is a critical mechanism underlying the enhanced toxicity of PS-NH 2 . Furthermore, PS-NH 2 –induced microglial cytotoxicity contributed to the secondary degeneration of surrounding neuronal cells. Treatment with Trolox, a vitamin E analog, attenuated microglial toxicity and neuronal loss through suppression of ROS-mediated inflammatory signaling, including reduced JNK phosphorylation, NLRP3 expression, and NF-κB p50 nuclear translocation. These results highlight the importance of surface chemistry in determining microplastic toxicity and indicate that amine modification substantially enhances the neuroinflammatory and neurotoxic potential of microplastics through pathways mediated by mitochondrial reactive oxygen and nitrogen species. These findings have important implications for assessing the risks of microplastics in neurological disorders and for developing strategies to mitigate their harmful effects.