Polystyrene Microplastics Disrupt the Gut-Brain Axis via Activating Brain TLR4 and Impair Hippocampal Synapses...

Polystyrene (PS) is one of the most widely used microplastics (MPs) globally. However, the neurotoxicity mechanisms triggered by polystyrene microplastics (PS-MPs) have yet to be elucidated. This study explored the damage induced by PS-MPs to the intestinal and central nervous system (CNS) and the potential mechanism. The results showed that PS-MPs exhibited size-dependent bioaccumulation with enhanced barrier penetration at submicron scales (500 nm > 1 μm ≫ 5 μm). Paradoxically, 1 μm PS-MPs demonstrated maximum neuroinflammation despite inferior biodistribution to 500 nm particles. Mechanistically, both sizes induce gut dysbiosis-mediated barrier disruption, elevating circulatory LPS that translocates across compromised BBB. This triggers excessive activation of the TLR4/MyD88/NF-κB pathway, subsequently inducing a surge in pro-inflammatory cytokines, ultimately leading to synaptic lesions in the hippocampal region. Our findings established smaller PS-MPs (≤1 μm) as latent neurodegeneration risk factors, demanding urgent assessment of chronic exposure consequences.