The Trojan horse effect of nanoplastics exacerbates methylmercury-induced neurotoxicity during zebrafish development

While the ability of plastic particles to transport heavy metals is well established, their Trojan horse effect on aquatic organisms remains debated, as they are suspected of facilitating the penetration of chemicals in tissues but also of reducing bioavailability and accelerating pollutant elimination. Here, we investigated the combined effects of 250 nm polystyrene nanoplastics (NPs) and methylmercury (MeHg) on zebrafish larvae over a 30-day exposure period. Larvae were exposed to 1000 μg/L NPs, 1 μg/L MeHg (MeHg1), 10 μg/L MeHg (MeHg10), or their respective combinations (Mix1 and Mix10). The presence of NPs enhanced MeHg accumulation and redirected its distribution toward the fish's head and eyes. On their own, NPs altered swimming activity, while MeHg10 induced mortality, reduced growth and diminished swimming activity. Proteomic analysis highlighted significant effects on lipid metabolism, oxidative stress, detoxification, myogenesis and catabolism. Although no light sensitivity deficits were detected through visual motor response testing, proteomic data suggested vision impairment in the mixture-exposed groups. High mortality rates were observed in Mix10-exposed fish, likely due to severe hypoactivity, which hindered feeding. This hypoactivity was linked to disrupted lipid metabolism, impaired neurotransmission, reduced ATP production, and neuroinflammation leading to neuronal degeneration. We concluded that the presence of NPs intensified MeHg neurotoxicity over a prolonged exposure, significantly increasing mortality.