Browsing by Author "Radzimirski, Anthony"

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    METHYLMERCURY ALTERATION IN THERMOGENESIS IS DIET DEPENDENT IN CAENORHABDITIS ELEGANS
    (2024-04-18) Varney, Abigail; Radzimirski, Anthony; Caito, Samuel
    Thermogenesis is the process by which adipocytes metabolize triglycerides (TAG) to release energy as heat. This process is disrupted in metabolic syndrome, leading to increased TAG levels and weight gain. Methylmercury (MeHg) is an environmental toxin that has both neurotoxic and metabolic effects. We have previously shown that MeHg disrupts lipid homeostasis, leading to increased TAG content and storage sites in Caenorhabditis elegans. Furthermore, we have shown that TAG content in response to MeHg is dependent on their Escherichia coli diet. Worms fed a low lipid containing strain (HT115) showed less lipid dysregulation than worms fed a high lipid containing strain (OP50). As we have seen accumulation of TAG in response to MeHg, we hypothesized that MeHg could reduce thermogenesis in C. elegans. Worms were treated with environmentally relevant doses of MeHg, fed either OP50 or HT115, and were grown to adulthood at 15 or 25˚C. Worms were then placed at 4˚C for 48 hours and scored for survival. Untreated worms maintained at 15˚C and fed either diet were able to survive the temperature shift. MeHg significantly decreased survival of worms fed OP50 diet following the 15 to 4˚C shift, suggesting that thermoregulation was inhibited by MeHg. In contrast, MeHg had minimal effects on the survival of worms fed HT115 diet following the 15 to 4˚C shift. Shifting worms from 25 to 4˚C is lethal to all worms fed OP50. However, the HT115 diet prevented lethality in untreated or MeHg treated worms shifted from 25 to 4˚C. These data suggest that the HT115 diet is protective and can induce thermogenesis. Heat generation derives from mitochondria. HT115 fed worms had improved mitochondrial health in response to MeHg than OP50 fed worms. Taken together, our data suggests that MeHg-dependent mitochondrial damage is diet dependent leading to alterations in thermogenesis.
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    SEROTONERGIC AND DOPAMINERGIC-DEPENDENT BEHAVIORS ARE ALTERED BY LANTHANIDE SERIES METALS IN Caenorhabditis elegans
    (2023-04-20) Radzimirski, Anthony; Ireland, Nicholas; Miller, Lydia; Croft, Michael; Newell-Caito, Jennifer; Caito, Samuel
    The lanthanide series elements are transition metals used as critical components of electronics, as well as rechargeable batteries, fertilizers, antimicrobials, contrast agents for medical imaging, and diesel fuel additives. Furthermore, as electronics are limited in lifespan, lanthanides are found in electronic waste. With the surge in their utilization, lanthanide metals are being found more in our environment. However, little is known about the health effects associated with lanthanide exposure. Epidemiological studies as well as studies performed in rodents exposed to lanthanum (La) suggest neurological damage, learning and memory impairment, and disruption of neurotransmitter signaling, particularly in serotonin and dopamine pathways. Unfortunately, little is known about the neurological effects of heavier lanthanides. As dysfunction of serotonergic and dopaminergic signaling are implicated in multiple neurological conditions, including Parkinson’s disease, depression, generalized anxiety disorder, and post-traumatic stress disorder, it is of utmost importance to determine the effects of La and other lanthanides on these neurotransmitter systems. We therefore hypothesized that early life exposure of light (La or cerium (Ce)) or heavy (erbium(Er) or ytterbium (Yb)) lanthanides in Caenorhabditis elegans could cause dysregulation of serotonergic and dopaminergic signaling upon adulthood. Serotonergic signaling was assessed by measuring pharyngeal pump rate, crawl-to-swim transition, as well as egg laying behaviors. Dopaminergic signaling was assessed by measuring locomotor rate, egg laying, and swim-to-crawl transition behaviors. Treatment with La, Ce, Er, or Yb caused deficits in serotonergic or dopaminergic signaling in all assays, suggesting both the heavy and light lanthanides disrupt these neurotransmitter systems. Concomitant with dysregulation of neurotransmission, all four lanthanides increased reactive oxygen species (ROS) generation, while decreased glutathione and ATP levels. This suggests increased oxidative stress, which is a known modifier of neurotransmission. Altogether, our data suggest that both heavy and light lanthanide series elements disrupt serotonergic and dopaminergic signaling and may affect the development or pharmacological management of related neurological conditions.
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    SYNERGISTIC NEUROTOXIC EFFECTS OF METHYLMERCURY AND PER-AND-POLYFLUOROALKYL SUBSTANCES (PFAS) IN CAENORHABDITIS ELEGANS
    (2024-04-18) Radzimirski, Anthony; Varney, Abigail; Ireland, Nicholas; Caito, Samuel
    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.