Polystyrene nanoplastics act as endocrine disruptors altering neurotransmitter levels and locomotor activity via estrogen receptor during early zebrafish development

Polystyrene nanoplastics (PSNPs) are emerging endocrine disruptors with significant neurotoxic potential. This study evaluates the impact of PSNP exposure on neurotransmitter levels, locomotor activity, and gene expression in zebrafish (Danio rerio) embryos and larvae, with a focus on estrogen receptor (ER) signaling pathways using the antagonist ICI 182,720 (ICI). Zebrafish embryos were exposed to varying PSNP concentrations (0.01, 0.1, 1, and 10 µg/mL) with or without 10 µM ICI co-incubation from 2 to 120 hpf. PSNP exposure significantly reduced TH-positive neuron area, increased apoptosis in the brain, impaired locomotor activity, and increased anxiety-like behavior. These effects were associated with downregulated dopaminergic gene expression (th1, th2, dat, ddc), upregulated apoptotic markers (tp53, casp3, casp9, bax), and decreased anti-apoptotic bcl2a expression. Additionally, PSNPs significantly reduced acetylcholinesterase (AChE) activity. Interestingly, co-incubation with ICI reversed neurotransmitter levels, reducing brain apoptosis, normalized locomotor responses, gene expression changes, and brought AChE activity back to control levels, indicating that the neurotoxic effects of PSNPs are mediated through ER pathways. This study provides evidence that PSNPs act as endocrine disruptors, interfering with neurotransmitter signaling, promoting brain apoptosis, and altering behavior via ER pathways during early zebrafish development.