Micro- and nanoplastic pollution poses a global threat due to environmental accumulation, poor reversibility, and adverse effects on humans and wildlife. Nanoplastics can cross the blood-brain barrier (BBB) and induce neurotoxicity, yet studies investigating the developmental effects of nanoplastic exposure during early life (a period vulnerable to environmental stressors) and their influence on later-life outcomes remain limited. This study examined whether early-life exposure to polystyrene nanoplastics (PS-NPs) during embryonic and larval stages has lasting effects and alters susceptibility to hexabromocyclododecane (HBCD), a brominated flame retardant globally detected in aquatic environment, in zebrafish. Developmental exposure to PS-NPs led to reduced locomotor activity in both larvae (5 dpf) and adults (157 dpf). Furthermore, early PS-NP exposure modified behavioral response to HBCD in adulthood: adult fish exposed to HBCD for the first time exhibited hyperactivity, whereas those previously exposed to PS-NPs showed no significant change. These differential responses were strongly correlated with altered expressions of neurological and neurodevelopmental genes (e.g., drd2a, glud1a, fezf2) and global DNA methylation levels. Our findings suggest that epigenetic processes may contribute to the observed differences in adult locomotor behavior and susceptibility to subsequent HBCD exposure. This study highlights the need for further research into locus-specific epigenetic regulation of neural genes during development and their quantitative relationship to adverse outcomes. In light of the conservation of epigenetic mechanisms across species and the widespread presence of environmental substances from industrial and consumer products that can disrupt these pathways, our study underscores the broader implications for environmental health.
