Journal of Clinical Toxicology

Journal of Clinical Toxicology
Open Access

ISSN: 2161-0495

+44 1478 350008

Methylmercury-induced dopaminergic neurotoxicity in Caenorhabditis elegans


International Toxicology Summit & Expo

November 26-28, 2012 Hilton San Antonio Airport, USA

Ebany Martinez-Finley

Scientific Tracks Abstracts: J Clinic Toxicol

Abstract :

M ercury is a persistent environmental contaminant that exerts its toxic effects on the nervous system through molecular mechanisms that remain unknown. Parkinson�s disease (PD) is a neurodegenerative disorder characterized by the slow progression and irreversible loss of the dopaminergic (DAergic) neurons. Epidemiological studies have pointed to the contribution of methylmercury (MeHg) to DAergic vulnerability and predisposition to PD. We examined the impact of early-life exposure to MeHg on DAergic neurodegeneration in Caenorhabditis elegans . SKN-1, orthologue of mammalian Nrf2, is a major stress- activated cytoprotective transcription factor. We hypothesized that MeHg�s toxicity is dependent on an intact SKN-1 response and skn-1 knockout (KO) worms would show heightened toxicity compared to wildtype (N2). We also tested the effect of MeHg in a pdr-1KO worm, ortholog to the human parkin gene (mutated form found in juvenile PD), under the premise that these worms would show heightened sensitivity to MeHg. We identified the impact of early-life MeHg exposure on MeHg content, stress reactivity and measures of DAergic neurodegeneration in N2, skn-1KO and pdr-1KO worms. Our data suggests that skn-1KO and pdr-1KO worms are more sensitive to MeHg than N2 controls. MeHg uptake was higher in the pdr-1KO strain compared to the N2 strain. DAergic morphology revealed presence of puncta in skn-1KOs and loss of cell body fluorescence in pdr-1KO. Dopamine (DA)-dependent behavioral analysis revealed alterations in DA following MeHg exposure, corroborated by decreased DA levels. Taken together this data suggests that exposure to MeHg early in the lifespan can have detrimental effects on DAergic neurons

Biography :

Ebany Martinez-Finley earned her Ph.D. in Biomedical Sciences with concentrations in Toxicology/Neuroscience from the University of New Mexico in 2010. She is currently a Postdoctoral fellow at Vanderbilt University Medical School in the laboratory of Dr. Michael Aschner. She sits on the Postdoctoral Assembly Board of the Society of Toxicology and is the Senior Co-Advisor to the Postdoctoral Association at Vanderbilt University

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