Unseen threats: How nanoplastics trigger anxiety and depression-like behaviors in zebrafish (Danio rerio)☆

Nanoplastics (NPs) are emerging contaminants of global concern, widely detected in water, air, and food, leading to continuous and largely unnoticed human and wildlife exposure. Despite increasing evidence of their neurotoxic potential, the mechanistic links between NP exposure and the development of neuropsychiatric disorders remain poorly understood. This study investigates whether early-life exposure to 20 nm polystyrene nanoplastics (PNPs) contributes to persistent behavioral and neurobiological changes associated with anxiety and depression. Zebrafish embryos were exposed to PNPs exclusively during early development and raised for six months before undergoing comprehensive behavioral, metabolomic, histopathological, immunohistochemical, and gene expression analyses. PNP-exposed fish exhibited lasting anxiety- and depression-like phenotypes, including heightened stress reactivity, disrupted circadian rhythms, increased social clustering, and altered locomotion. Multi-omics analyses revealed neurotransmitter imbalance, oxidative stress signatures, neuronal degeneration, and apoptotic activation in brain tissues, alongside stress-axis hyperactivation and impaired antioxidant defenses at the transcriptional level. Together, these findings provide mechanistic evidence that early-life NP exposure may be an overlooked environmental risk factor for anxiety and depression. By integrating behavioral and molecular endpoints in a translational zebrafish model, this study underscores the urgent need for global monitoring of nanoplastic contamination and its potential implications for human mental health.