Related Experiment Video
Updated: Mar 26, 2026
Quantifying Levels of Dopaminergic Neuron Morphological Alteration and Degeneration in Caenorhabditis elegans
Published on: November 20, 2021
NAD+ Supplementation Attenuates Methylmercury Dopaminergic and Mitochondrial Toxicity in Caenorhabditis Elegans
Samuel W Caito1, Michael Aschner2
1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461.
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.
Insights
Methylmercury (MeHg) exposure depletes nicotinamide adenine dinucleotide (NAD(+)) levels, causing neurotoxicity. Supplementing NAD(+) protects against MeHg-induced damage and may prevent Parkinson
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Methylmercury (MeHg) is a neurotoxin found in seafood, linked to Parkinson's disease-like dopaminergic (DAergic) dysfunction.
- Previous research demonstrated MeHg induces morphological and behavioral changes in C. elegans DAergic neurons, associated with oxidative stress.
Purpose of the Study:
- To investigate the impact of MeHg on cellular nicotinamide adenine dinucleotide (NAD(+)) levels.
- To determine if NAD(+) supplementation can prevent MeHg-induced neurotoxicity and associated pathologies.
Main Methods:
- Treatment of Caenorhabditis elegans with MeHg and NAD(+) supplementation.
- Assessment of cellular NAD(+) levels, DAergic neuron integrity, and DAergic-dependent behaviors.
- Analysis of MeHg toxicity in a mutant C. elegans strain with impaired NAD(+) synthesis.
Main Results:
- MeHg exposure led to depletion of cellular NAD(+) levels in C. elegans.
- NAD(+) supplementation prior to MeHg exposure prevented NAD(+) depletion, DAergic neurodegeneration, and behavioral deficits.
- A mutant C. elegans strain unable to synthesize NAD(+) exhibited increased sensitivity to MeHg toxicity.
- NAD(+) supplementation protected against MeHg-induced oxidative stress and mitochondrial dysfunction.
Conclusions:
- Cellular NAD(+) levels are critical in the response to Methylmercury exposure.
- NAD(+) supplementation demonstrates potential therapeutic benefits for MeHg toxicity.
- NAD(+) supplementation may offer a protective strategy against Parkinson's disease-related cellular damage.
