Adverse effects of bifenthrin exposure on neurobehavior and neurodevelopment in a zebrafish embryo/larvae model

Bifenthrin, a third-generation synthetic pyrethroid, is widely used as an agricultural insecticide. However, it can flow into surface and groundwater, leading to adverse consequences such as immunotoxicity, hepatotoxicity, hormone dysregulation, or neurotoxicity. Nevertheless, the entire range of its neurotoxic consequences, particularly in aquatic organisms, remains unclear. In this study, we conducted an extensive examination of how exposure to bifenthrin affects the behavior and nervous system function of aquatic vertebrates, using a zebrafish model and multiple-layered assays. We exposed wild-type and transgenic lines [tg(elavl3:eGFP) and tg(mbp:mGFP)] to bifenthrin from <3 h post-fertilization (hpf) to 120 hpf. Our findings indicate that bifenthrin exposure concentrations of 103.9 and 362.1 μg/L significantly affects the tail-coiling response at 24 hpf and the touch-evoked responses at 72 hpf. Moreover, it has a significant effect on various aspects of behavior such as body contact, distance between subjects, distance moved, and turn angle. We attribute these effects to changes in acetylcholinesterase and dopamine levels, which decrease in a concentration-dependent manner. Furthermore, neuroimaging revealed neurogenesis defects, e.g., shortened brain and axon widths, and demyelination of oligodendrocytes and Schwann cells. Additionally, the transcription of genes related to neurodevelopment (e.g., gap43, manf, gfap, nestin, sox2) were significantly upregulated and neurotransmitters (e.g., nlgn1, drd1, slc6a4a, ache) was significantly downregulated. In summary, our data shows that bifenthrin exposure has detrimental effects on neurodevelopmental and neurotransmission systems in the zebrafish embryo/larvae model.