Titanium Dioxide Nanoparticles Aggravated the Developmental Neurotoxicity of Ammonia Nitrogen on Zebrafish Embryos

Total ammonia nitrogen (TAN) is a common and potent neurotoxic pollutant in aquatic environments. Due to their strong adsorption capacity, titanium dioxide nanoparticles (n-TiO₂), a widely used engineered material, can induce combined toxicity with multiple pollutants. However, the combined neurotoxicity of n-TiO₂ and TAN and its underlying mechanisms remain unclear. In this study, zebrafish embryos were exposed to TAN (0, 0.1, 1, 10 mg/L) and n-TiO₂ (100 µg/L) individually or in combination for 120 h. The results indicated that co-exposure to n-TiO₂ and TAN significantly increased the bioaccumulation of TAN in zebrafish embryos compared to TAN alone. Consequently, this led to exacerbated neurotoxicity, manifested as developmental impairments and abnormal motor behavior. Mechanistic investigations revealed that the co-exposure aggravated developmental neurotoxicity by triggering neuronal apoptosis and oxidative stress, disrupting the cholinergic and dopaminergic systems, and impairing neural and retinal development. Transcriptomic analysis further indicated that the co-exposure predominantly perturbed neurodevelopment, oxidative stress, and apoptosis. In conclusion, this study confirms that n-TiO₂ significantly amplifies TAN-induced neurodevelopmental toxicity by promoting its bioaccumulation and synergistically disrupting multiple neurophysiological processes. These findings provide crucial scientific evidence for assessing the combined ecological risks of nanomaterials and conventional pollutants.