Genetic factors in methylmercury-induced neurotoxicity: What have we learned from Caenorhabditis elegans models?

Caenorhabditis elegans (C. elegans) is a microscopic-scale worm that is used as a model organism to investigate genetics, developmental biology and neuroscience, to name a few. The increased numbers of research tools in this animal have driven the use of the model in a wide spectrum of research areas, including the neurotoxicology of mercury (Hg), especially methylmercury (MeHg). Recent advances have shown that the C. elegans model of MeHg-induced toxicity can provide novel insights on how the toxic effects of MeHg are modulated by genetic factors. These studies involve multiple exposure paradigms and various endpoints, including metabolism, dopaminergic neurotoxicity, mitochondrial health and reproductive toxicity. The accumulated evidence strongly supports the notion that the C. elegans model is indispensable for our general understanding of the nervous systems and organisms' responses and strategies for the handling of overexposure to MeHg. In the current review, we surveyed the studies on MeHg toxicity in C. elegans with a focus on antioxidant responses, sex-specific toxicity, transgenerational toxicity, and neurodegeneration. We also analyzed current research trends and the knowledge gaps to be filled in future studies. We conclude that C. elegans models of MeHg toxicity bolster efforts to investigate mechanisms underlying environmental exposures at early developmental stages and in age-related disorders.