Integrate transcriptomic and metabolomic analysis reveals the underlying mechanisms of behavioral disorders in zebrafish (Danio rerio) induced by imidacloprid.

Imidacloprid, a widely used neonicotinoid insecticide, poses a significant threat to aquatic ecosystems. Behavior is a functional indicator of the net sensory, motor, and integrative processes of the nervous system and is presumed to be more sensitive in detecting toxicity. In the present study, we investigated the behavioral effects of imidacloprid at the level of environmental concentrations (1, 10 and 100 μg/L) for a constant exposure to zebrafish adults, and performed the integrated transcriptomic and metabolomic analysis to analyze the molecular mechanism underlying behavioral effects of imidacloprid. Our results show that imidacloprid exposure significantly induce behavioral disruptions characterized by anxiety, depression, and reduced physiological function including exploratory, decision, social interaction and locomotor activity. Integrated transcriptomic and metabolomic analysis indicate that the disruption of circadian rhythm, metabolic imbalance of arginine and proline, and neurotransmitter disorder are the underlying molecular mechanisms of behavioral impairment induced by imidacloprid. The "gene-metabolite-disease" network consisted by 11 metabolites and 15 genes is associated human disease Alzheimer's disease (AD) and schizophrenia. Our results confirm the behavioral impairment induced by imidacloprid at environmental concentrations for constant exposure. The identified genes and metabolites can be used not only to illustrate the underlying mechanisms, but also can be developed as biomarkers in determining the ecological risk of imidacloprid to aquatic organisms even Homo sapiens.