Selenomethionine-induced neurotoxicity and behavioural alterations in larval zebrafish (Danio rerio)

Selenium (Se) plays a crucial role in fishes, but even a slight increase beyond physiological levels can make it highly toxic. In contaminated environments, fishes primarily accumulate Se as selenomethionine (SeMet). While pernicious effects of SeMet in adult fishes are well-documented, its embryotoxicity, beyond teratogenic outcomes, are underexplored. In current study, 2 h post fertilized (hpf) zebrafish embryos were subjected to waterborne Se at sub-lethal concentrations (0 [control], 5, 10, and 25 µg/L; as SeMet) until 5 days post-fertilization (dpf). Results revealed that SeMet exposure at 10 and 25 µg/L significantly increased larval mortality and deformity rates compared to the control group. Moreover, SeMet exposure (5 and 10 µg/L Se) impaired thigmotactic and reflexive behaviours at 5 dpf. Embryonic SeMet exposure also resulted in an escalation in reactive oxygen species levels and apoptosis with elevating concentration, along with dysregulation of proteins and genes related to nervous system development including dopaminergic, serotonergic, and cholinergic signaling pathways at 5 dpf. Interestingly, pretreatment with N-acetylcysteine (NAC), a potent antioxidant, resulted in amelioration of SeMet-induced oxidative stress, apoptosis, molecular and behavioural deficits, suggesting that oxidative stress is an initiating mediator in triggering neurobehavioural impairments in larval zebrafish. Overall, this study highlights that neurobehavioural responses are more sensitive to SeMet than its teratogenic effects in larval zebrafish, thus providing novel perspectives on the developmental toxicity of Se in fish.