Neurotoxicity induced by combined exposure of microcystin-LR and nitrite in male zebrafish (Danio rerio): Effects of oxidant-antioxidant system and neurotransmitter system

Abstract

With the intensification of water eutrophication around the world, cyanobacterial blooms have been becoming a common environmental pollution problem. The levels of microcystin-LR (MC-LR) and nitrite rise sharply during the cyanobacterial bloom period, which may have potential joint toxicity on aquatic organisms. In this study, adult male zebrafish were immersed into different joint solutions of MC-LR (0, 3, 30 μg/L) and nitrite (0, 2, 20 mg/L) for 30 days to explore the neurotoxic effects and underlying mechanisms. The results showed that single factor MC-LR or nitrite caused a concentration-dependent damage in brain ultrastructure and the effects of their joint exposure were much more intense. Downregulated expression of mbp and bdnf associated with myelination of nerve fibers further confirmed that MC-LR and nitrite could damage the structure and function of neuron. The decreases in dopamine content, acetylcholinesterase activity and related gene mRNA levels indicated that MC-LR and nitrite adversely affected the normal function of the dopaminergic and cholinergic systems in zebrafish brain. In addition, the significant increase in malondialdehyde content suggested the occurrence of oxidative stress caused by MC-LR, nitrite and their joint-exposure, which paralleled a significant decrease in antioxidant enzyme‑manganese superoxide dismutase activity and its transcription level. In conclusion, MC-LR + Nitrite joint-exposure has synergistic neurotoxic effects on the structure and neurotransmitter systems of fish brain, and antioxidant capacity disruption caused by these two factors might be one of the underlying synergistic mechanisms. Therefore, there is a risk of being induced neurotoxicity in fish during sustained cyanobacterial bloom events.