Chronic dietary exposure to arsenic at environmentally relevant concentrations impairs cognitive performance in adult zebrafish (Danio rerio) via oxidative stress and dopaminergic dysfunction

The current study was designed to evaluate the effects of chronic dietary arsenic exposure on the cognitive performance of adult zebrafish and uncover probable pathways by which arsenic mediates such neurotoxic effects. Adult zebrafish were treated with 3 different dietary arsenic concentrations (30, 60, and 100 mu g/g dry weight (dw), as arsenite) in addition to control for 60 days. A latent learning paradigm, which employs a complex maze, was used to assess the cognitive performance of fish. Our results demonstrated that dietary treatment with arsenic, especially at medium (60 mu g/g dw) and high (100 mu g/g dw) exposure dose levels, significantly impaired the performance of fish in various latent learning tasks evaluated in the present study. Concomitant with cognitive dysfunction, chronic dietary exposure to arsenic was also found to increase arsenic accumulation and dopamine levels, and induce oxidative stress (reduced thiol redox, increased lipid peroxidation and expression of antioxidant enzyme genes) in the brain of zebrafish in a dose-dependent manner. Dopaminergic system in the brain is known to play a critical role in regulating cognitive behaviours in fish, and our observations suggested that chronic dietary treatment with medium and high arsenic doses leads to significant alterations in the expression of genes involved in dopamine signaling (dopamine receptors), synthesis (thyroxine hydroxylase) and metabolism (monoamine oxidase) in the zebrafish brain. Moreover, we also recorded significant downregulation of genes such as the brain-derived neurotrophic factor (BDNF) and ectonucleotidases (entpd2_mg, entpd2_mq, and 5 '-nucleotidase), which are critical for learning and memory functions, in the zebrafish brain following chronic dietary exposure to arsenic. Overall, the present study suggests that chronic environmentally relevant dietary exposure to arsenic can impair the cognitive performance in zebrafish, essentially by inducing oxida-tive stress and disrupting the dopaminergic neurotransmission in the brain.