Life cycle exposure to differentially charged polystyrene nanoplastics leads to gender-specific particle accumulation and neurotoxicity in zebrafish (Danio rerio)

Nanoplastics (NPs) have been widely detected in freshwater environments and photodegradation, as well as physical and chemical breakdown, lead to different surface charges on the plastics. Although evidence in the literature highlights the importance of NPs surface charge to neurotoxicity, substantial gaps in mechanistic understanding remain. In the current study, zebrafish (Danio rerio) were exposed to differentially charged NPs (PS, PS-NH₂, PS-COOH) at environmentally relevant concentration (10 μg/L). After full life cycle exposure, the potential neurotoxicity, brain damage, and the altered brain metabolism was investigated through light sheet microscopy 3-dimensional imaging, histopathology, Evans blue dye (EBD) extravasation, gene expression, and untargeted and targeted metabolomics of brain tissue in zebrafish. Exposure to PS, PS-NH₂, PS-COOH caused adverse effects on the performance of neurobehaviors, blood-brain-barrier (BBB) permeability, amino acid metabolism, damage to the BBB and mitochondria, and overt inflammatory response. PS-NH₂ (4.56-fold) and PS-COOH (3.59-fold) accumulated in the reticular formation (RF) of the male brain, while only PS-NH₂ was detected in the RF (6.57-fold) and ventral hypothalamus (Hv) (3.08-fold) of female brains. Several important biological pathways were negatively impacted in a charge- and gender-specific fashion. This study provides novel insights into the underlying toxicity mechanisms of differentially charged NPs in a model aquatic species, as well as the associated environmental risks of this important group of emerging contaminants.