Murine hippocampal CA3 vulnerability to intravenously administered polystyrene nanoplastics: preferential accumulation and ROS-related neuronal cell death.

Polystyrene nanoplastics (PS-NPs) are emerging neurotoxicants with the potential to access the brain following systemic exposure; however, their region-specific effects and underlying mechanisms remain incompletely understood. In this study, adult male mice (C57BL/6J) were intravenously injected with unlabeled or fluorescently labeled PS-NPs (50-60 nm) at a dose of 400 mg/kg, and brain tissues were collected and analyzed 3 days post-injection to evaluate PS-NPs distribution, oxidative stress, and regulated cell death pathways. Confocal imaging revealed preferential accumulation of fluorescent PS-NPs in the hippocampal CA3 region, where neuronal localization was most prominent among the regions examined. This accumulation was associated with a significant reduction in NeuN-positive neurons in CA3 (p < 0.01), accompanied by elevated mitochondrial ROS levels as detected by MitoSOX staining (p < 0.001). Immunofluorescence analyses demonstrated increased expression of cleaved caspase-3 and p-MLKL, indicating activation of apoptosis and necroptosis, whereas NLRP3 expression remained unchanged. Behavioral assessments using the Y-maze and passive avoidance tests revealed impairments in hippocampus-dependent cognitive performance in PS-NP-treated mice. Collectively, these findings suggest that acute intravenous exposure to PS-NPs induces early, region-selective neuronal vulnerability in the hippocampal CA3 area, which is associated with oxidative stress-mediated neuronal cell death and cognitive dysfunction under the present experimental conditions.