Publication: SYNERGISTIC NEUROTOXIC EFFECTS OF METHYLMERCURY AND PER-AND-POLYFLUOROALKYL SUBSTANCES (PFAS) IN CAENORHABDITIS ELEGANS
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Date
2024-04-18
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Abstract
Methylmercury (MeHg) is a well-known neurotoxic metal that is a major contaminant of our fish supply. Developmental exposure to MeHg causes cognitive and behavioral dysfunction in children, and cumulative exposure to MeHg has been linked to the development of neurodegenerative diseases, such as Parkinson’s disease. Recently, it has been determined that fish are becoming increasingly contaminated with per- and polyfluoroalkyl substances (PFAS). PFAS are a group of amphipathic compounds which have been used in industry for their unique property to repel both water and oils. While specific PFAS have been phased out of use and production in the United States, the environmental degradation of PFAS is slow. Both MeHg and PFAS have similar characteristics, particularly bioaccumulation and biomagnification up the food chain, ability to accumulate in the brain, and alteration in synaptic transmission of glutamate and dopamine. We therefore hypothesized that MeHg and PFAS co-exposures may synergize and produce more damage to the dopaminergic and glutamatergic nervous systems in Caenorhabditis elgans than single exposures alone. Worms were treated for 72 hours with increasing concentrations of PFOS, PFOA, or PFBS in the presence or absence of a low nontoxic dose of MeHg. Dose-response curves were generated and the lethal dose 50 (LD50) were calculated for each curve. Co-exposure of MeHg with either of the PFAS compounds shifted the dose-response curve to the left of the dose-response curve for PFAS. This suggests that the co-exposure was more toxic than PFAS exposure in worms. Glutamatergic and dopaminergic behaviors were assayed in worms treated with MeHg, PFAS, or MeHg + PFAS combination. For both behaviors, the co-exposure caused more behavioral deficits than MeHg or PFAS alone. Furthermore co-exposure to PFAS and MeHg altered both dopamine and glutamate neurotransmitter content. Taken together, our results suggest that there is a synergistic relationship between exposure to MeHg and PFAS compounds in C. elegans.