Neurotoxic effects of spirotetramat in zebrafish (Danio rerio): Brain injury, locomotor abnormalities, and altered visual-related pathways

Spirotetramat, a broad-spectrum tetronic acid insecticide, is widely used in agriculture because of its high insecticidal efficacy. However, its intensive and prolonged use may result in environmental accumulation and potential risks to non-target organisms. Although previous studies have demonstrated that spirotetramat induces developmental, reproductive, and hepatic toxicity in zebrafish, its neurotoxic effects on the brain and the underlying mechanisms remain poorly understood. Therefore, this study aimed to systematically evaluate the neurotoxicity of spirotetramat in zebrafish and to explore the potential molecular mechanisms involved.Histopathological examination, behavioral analysis, neurotransmitter quantification, transcriptomic profiling, and molecular docking were performed. Spirotetramat exposure caused obvious histopathological damage in the zebrafish brain, including vacuolation and cellular degeneration, and induced abnormal locomotor behaviors, as evidenced by increased swimming speed and distance, together with enhanced thigmotaxis, geotaxis, and scototaxis. In addition, spirotetramat disrupted neurotransmitter homeostasis, characterized by elevated DOPAC and HK levels and reduced Pun levels. Transcriptomic analysis revealed significant alterations in pathways related to visual transduction and neural regulation, accompanied by upregulated expression of key visual genes, including rho , pde6a , and saga . Molecular docking suggested potential interactions between spirotetramat and visual-related proteins in both zebrafish and humans. Overall, spirotetramat exerts significant neurotoxic effects in zebrafish, which may be associated with disruption of neurotransmitter homeostasis and visual-related signaling pathways. These findings provide new insights into the neurotoxic potential of spirotetramat and provide a basis for future experimental investigation of its ecological and potential human health risks.