Early-Life Iron Overload Disrupts Dopaminergic Neuron Function and Neurobehaviour in Zebrafish

Iron is an essential trace metal in vertebrates, but excess free iron can induce oxidative damage such as lipid peroxidation and, eventually, cell death. The central nervous system, with its high lipid content and oxygen consumption, is particularly susceptible to iron-mediated oxidative stress. The current study investigated the immediate and long-term effects of early-life iron exposure on neurobehavioural functions in developing zebrafish (Danio rerio). Zebrafish embryos were exposed to varying concentrations of iron from 0 to 5 days post-fertilization (dpf). The effects of iron treatments were investigated at 5 dpf (larval stage) and 21 dpf (juvenile stage). Behavioural assays revealed that iron exposure significantly reduced larval locomotor activity and impaired non-associative learning in a concentration-specific manner at 5 dpf. Increases in lipid peroxidation, apoptotic events, and disrupted dopaminergic system suggested that damage to dopaminergic circuits was likely associated with these behavioural deficits. While changes in larval behaviour were no longer observed at 21 dpf, fish exposed to high concentration of iron still experienced a significant elevation in lipid peroxidation. This was accompanied by potential compensatory responses, including changes in mRNA expression levels of genes associated with oxidative stress and free-iron clearance. These findings highlight the persistent consequences of early-life iron exposure in zebrafish and suggest transcriptional regulations as part of the defence mechanism against iron-induced neurotoxicity.