title: NAD+ Supplementation Attenuates Methylmercury Dopaminergic and Mitochondrial Toxicity in Caenorhabditis Elegans.
abstract: Methylmercury (MeHg) is a neurotoxic contaminant of our fish supply that has been linked to dopaminergic (DAergic) dysfunction that characterizes Parkinson's disease. We have previously shown that MeHg causes both morphological and behavioral changes in the Caenorhabditis elegans DAergic neurons that are associated with oxidative stress. We were therefore interested in whether the redox sensitive cofactor nicotinamide adenine dinucleotide (NAD(+)) may be affected by MeHg and whether supplementation of NAD( + )may prevent MeHg-induced toxicities. Worms treated with MeHg showed depletion in cellular NAD( + )levels, which was prevented by NAD( + )supplementation prior to MeHg treatment. NAD( + )supplementation also prevented DAergic neurodegeneration and deficits in DAergic-dependent behavior upon MeHg exposure. In a mutant worm line that cannot synthesize NAD( + )from nicotinamide, MeHg lethality and DAergic behavioral deficits were more sensitive to MeHg than wildtype worms, demonstrating the importance of NAD( + )in MeHg toxicity. In wildtype worms, NAD( + )supplementation provided protection from MeHg-induced oxidative stress and mitochondrial dysfunction. These data show the importance of NAD( + )levels in the response to MeHg exposure. NAD( + )supplementation may be beneficial for MeHg-induced toxicities and preventing cellular damage involved in Parkinson's disease.
authors: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461.
authors: Samuel W
authors: SW
authors: Caito
authors: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461 michael.aschner@einstein.yu.edu.
authors: Michael
authors: M
authors: Aschner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D008767:Methylmercury Compounds / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009243:NAD / Q000494:pharmacology*; D009410:Nerve Degeneration; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010641:Phenotype
chemical_list: D008767:Methylmercury Compounds; D009243:NAD
keywords: C. elegans; dopaminergic neurons; methylmercury; mitochondria