Polystyrene nanoplastics induce cognitive dysfunction and dendritic spine deterioration via excessive mitochondrial fission

Our research addresses the critical issue of polystyrene nanoplastics (PS-NPs) exposure and their neurotoxic effects, highlighting a significant environmental health concern. We proved that PS-NPs could breach the blood-brain barrier (BBB) and accumulate in murine brains, emphasizing the need for further investigation into their impact on human health. Using both in vivo models with Thy1-GFP-M transgenic mice and in vitro models with primary hippocampal neurons, we explored the effects of PS-NPs on cognitive function and neuroplasticity. Our results revealed that PS-NPs lead to cognitive impairment, evidenced by impaired performance in behavioral tests. Additionally, PS-NPs caused a significant reduction in dendritic spine density and altered the morphology of spines in hippocampal CA1 neurons. We explored the underlying mechanisms, finding that PS-NPs induced mitochondrial dysfunction, characterized by decreased membrane potential, reduced ATP production, and excessive mitochondrial fission. This mitochondrial disruption was associated with excessive mitophagy. Importantly, Mitochondrial Division Inhibitor-1 (Mdivi-1) treatment alleviated the neurotoxic effect, stabilized mitochondrial function, maintained dendritic spine density, and reversed the cognitive impairment induced by the PS-NPs. Overall, our study highlights the significant neurotoxic potential of PS-NPs and suggests that targeting mitochondrial fission can be a viable therapeutic strategy. This work underscores the urgent need to understand the neurological consequences of NPs exposure and develop strategies to counteract their health risks. • PS-NPs accumulate in hippocampal neurons and leading to cognitive dysfunction. • PS-NPs exposure reduce dendritic spine density and mature mushroom-type spines. • PS-NPs induce mitochondrial dysfunction, decrease membrane potential, ATP levels, and increase mitochondrial fission. • Mdivi-1 treatment reverses PS-NPs induced mitochondrial and dendritic spine deterioration, restoring neuronal health.