Polystyrene microplastics induce depression-like behavior in zebrafish via neuroinflammation and circadian rhythm disruption

Polystyrene microplastics (PS-MPs) are widespread pollutants in aquatic environments that accumulate in various organs, including the brain, raising concerns about their neurotoxic effects. This study exposed zebrafish to environmentally relevant concentrations (25 and 250 μg/L) of PS-MPs for 40 days to investigate their impact on neurobehavior and underlying mechanisms. Results revealed that PS-MPs induced depression-like behaviors in zebrafish, characterized by reduced exploration, decreased locomotor activity, and altered social interaction. Histological analyses of brain tissue demonstrated PS-MPs-induced neuropathological changes, including perinuclear vacuolation and reduced Nissl bodies. Additionally, PS-MPs triggered neuroinflammation, evidenced by upregulated pro-inflammatory cytokines (il-6, il-1β), and disrupted the circadian rhythm, leading to altered expression of key clock genes (per1b, per2, per3) and cryptochrome genes (cry1a, cry2). Furthermore, PS-MPs exposure significantly altered neurotransmitter levels, decreasing dopamine, serotonin, norepinephrine, acetylcholine, tyrosine, and tryptophan. In vitro experiments using HMC3 microglia cells confirmed that PS-MPs induced microglial activation, morphological changes, and dysregulated gene expression related to inflammation and circadian rhythm. These findings provide compelling evidence that PS-MPs induce depression-like behaviors in zebrafish through mechanisms involving neuroinflammation, circadian rhythm disruption, and neurotransmitter imbalances, highlighting the potential ecological risks of PS-MPs and contributing to our understanding of the neurotoxicity of microplastics.