Combined neurotoxicity of aged polystyrene microplastics and cadmium in zebrafish: A gut-brain axis perspective.

Abstract

Microplastics (MPs) can adsorb environmental pollutants, leading to co-toxicity in aquatic organisms. Aged MPs (AMPs) exhibit enhanced adsorption capacity, exacerbating combined toxicity with environmental pollutants. To investigate the neurotoxicity of polystyrene MPs (PS), aged PS (APS), and cadmium (Cd), and explore mechanisms from the gut-brain axis, zebrafish were exposed to PS or APS (200 μg/L) and Cd (10 μg/L), single or in combination, for 21 days. Results showed that co-exposure to APS and Cd caused the most severe neurotoxicity, correlated with significant Cd accumulation in the brain and disruption of the gut-brain axis. APS + Cd exposure led to altered gut metabolism, especially in biotin and arginine biosynthesis pathways, may contribute to oxidative stress and inflammation in the gut. Gut metabolites associated with neurotransmitter synthesis (choline and dopamine) were significantly reduced. These gut changes decreased cldn5a expression, may disrupted the blood-brain barrier and triggered oxidative stress, inflammation, and impaired neurotransmitter synthesis in the brain, thereby playing a role in neurotoxicity. Furthermore, transcriptome analysis revealed significant enrichment of differentially expressed genes in the neuroactive ligand-receptor interaction, apoptosis, and lipid metabolism pathways, suggesting neuronal cell damage. This study provides a scientific basis for assessing the combined neurotoxicity and mechanisms of MPs and heavy metals.

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