Effects of Global DNA Methylation Changes on Neurobehavior in Zebrafish

Abstract

A number of environmental neurotoxicants modulate DNA methylation, but its influence on neurobehavior remains unclear. The laboratory has established that low-level developmental methylmercury exposure induces neurobehavioral deficits; the current results demonstrate that it also induces global DNA hypomethylation. DNA methyltransferase 1-mutant zebrafish (exhibit ~70% reduction in enzymatic activity) were used to assess the role of DNA hypomethylation on behavior. Several neurobehavioral assays including the C-start escape, circadian rhythm, basic locomotion and visual-motor response (VMR) were also performed. There was a significant difference in VMR between the wild type and mutant animals. Other behavior assays revealed no significant difference, primarily due to small sample size, but several trends were observed. Mutants demonstrated a lack of persistent circadian rhythms when held in constant low light, and were hyperactive under normal lighting conditions. In conclusion, toxicant-induced global hypomethylation of DNA may alter neurobehavior in morphologically normal eleutheroembryos and the mechanism needs further investigation.