FGF1 alleviates polystyrene nanoplastics-induced neuroinflammation through the suppression of lipophagy.

Global contamination with nanoplastics (NPs) has raised public concern regarding their adverse effects on human health. However, little is known about the toxic effects of NPs on the nervous system. This study explored the neurotoxicity of polystyrene nanoplastics (PS-NPs) under the exposure model in vitro and in vivo. The results showed that environmentally relevant PS-NPs exposure activated lipophagy-related lipolysis. This activation promoted the production of lipid inflammatory mediators 2-arachidonoylglycerol (2-AG) and prostaglandin E2 (PGE2), thereby driving neuroinflammation in vitro. RNA sequencing revealed that fibroblast growth factor (FGF1) was negatively associated with the activation of lipophagy. Exogenous treatment with FGF1 inhibited PS-NPs-induced neuroinflammation and lipid accumulation in vitro and in vivo via the suppression of lipophagy. In addition, exogenous treatment with FGF1 alleviated PS-NPs-induced learning and memory deficits and neuropathological injury in mice. Our results provided new insights into the neurotoxicity effects and mechanisms of PS-NPs. Meanwhile, we found that FGF1 is a potential neuroprotective factor against PS-NPs-induced neurological injury by remodeling lipid metabolism in the central nervous system.