Polystyrene Nanoplastics Accumulate in Murine Cortex and Induce Transient Microglial Activation via Endolysosomal Retention

Abstract

Environmental degradation and accumulation of plastics results in micro- and nanoplastics (MNPLs) that are small enough to cross biological barriers, including the blood-brain barrier. Microglia, resident immune cells of brain, are critical regulators of neuroimmune homeostasis and represent a cellular target of nanoplastic exposure. In this study, we assessed the neurotoxic effects of two sizes of polystyrene nanoplastics (PS-NPs; 100 nm and 500 nm) using integrated in vivo and in vitro exposure and washout paradigms. In vivo exposure in mice (60 days; 0.15 or 1.5 mg/day) showed the accumulation of both PS-NP sizes in the cerebral cortex without histopathological damage. However, cortical microglia showed pronounced morphological remodeling, observed as increased expression of Iba1 and GFAP. Transcriptomic profiling of cortical tissue revealed a strong size-dependent response. The 100 nm PS-NP group revealed 18 DEGs (|log2FC| [≥] 2, padj View larger version (27K): org.highwire.dtl.DTLVardef@466df4org.highwire.dtl.DTLVardef@1dcb163org.highwire.dtl.DTLVardef@21916org.highwire.dtl.DTLVardef@1bcf775_HPS_FORMAT_FIGEXP M_FIG C_FIG