Effects of di-(2-ethylhexyl) phthalate (DEHP) on behavior and dopamine signaling in zebrafish (Danio rerio)

Abstract

Di (2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer, also known as a developmental toxicant, but its neurobehavioral toxicity remains elusive. This study evaluated the neurobehavioral toxicity and its possible mechanism in larval zebrafish. Embryos at gastrula period (~6 h post fertilization, hpf) were exposure to DEHP (0, 1, 2.5, 5 and 10 mg/L) for 7 days. Spontaneous tail movement in embryos and swimming activity in larvae were monitored. Alterations in the mRNA expression of genes involved in dopamine signaling and apoptosis pathway were assessed. In situ apoptotic cells were assessed by Acridine orange staining, and oxidative damage were measured using enzymatic assay. The behavior results showed that DEHP inhibited spontaneous tail movement and decreased locomotor activities in the light/dark behavioral test. Meanwhile, behavioral changes were accompanied by increased apoptosis and malondialdehyde (MDA) content, decreased superoxide dismutase (SOD) activity and dopamine (DA) content, and perturbed the expression of genes associated with the synthesis (th), reuptake (dat) and metabolism (mao) of DA, with dopamine receptors (DRs), and with the apoptosis pathway (p53, bax, bcl2, caspase-3, caspase-8, caspase-9). The findings will help to illuminate the possible neurobehavioral toxicity mechanisms of organism exposure to DEHP.