Hexavalent chromium neurotoxicity in Caenorhabditis elegans targeted GABAergic, cholinergic, and dopaminergic...

Hexavalent chromium [Cr(VI)] is a ubiquitous environmental pollutant and potent toxicant. Cr(VI) exposure impacts millions of people around the world, primarily through inhalation or ingestion. Such exposures are best known for contributing to cancers of the lung, sinus, and nasal passage, damage to kidneys and liver, and contact dermatitis. Growing evidence indicates exposure contributes to neurological conditions, but knowledge gaps persist regarding Cr(VI) neurotoxicity. Human studies report Cr(VI) contributes to autism spectrum disorders, motor neuron disease, olfactory dysfunction, and impaired memory. However, knowledge of specific targets for Cr(VI) in the brain is limited to reports of regional accumulation (greatest effects reported in the rodent hippocampus, hypothalamus, and pituitary gland), while cell-specific effects remain unknown. Caenorhabditis elegans is a useful high-throughput model, frequently used for metals neurotoxicity. Here, we characterize a C. elegans model to address knowledge gaps in Cr(VI) neurotoxicity. All Cr(VI) concentrations tested were sublethal, and we estimate bioaccumulation of Cr in worms was ∼1e10^-8% of the administered dose after a 24-hour exposure. Cr(VI) initially targeted GABAergic neurons after a 6-hour exposure, while cholinergic, dopaminergic, and GABAergic neurons were affected following a 24-hour exposure. Impacts on behaviors were consistent with neurodegeneration. Further, Cr(VI) exacerbated gut autofluorescence in worms, indicative of accelerated biological aging. These data collectively address key knowledge gaps, identifying key neuronal targets and informing potential mechanisms of neurotoxicity.