Polystyrene nanoplastics induce cognitive dysfunction and dendritic spine deterioration via excessive mitochondrial fission
Hongxiang Yu, Lingting Jin, Ying Zi, Jing Lu, Ye Long, Ran Xiong, Bei Zhang
Abstract
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.