We are interested in understanding how changes in neurotransmitter release affect sensitivity of Caenorhabditis elegans to oxidative stress. Oxidative stress can occur when cells fail to neutralize reactive oxidative species. Nucleic acids, lipids, and proteins can be damaged in response to oxidative stress and affected neurons may undergo neurodegeneration. Activity in neurons can confer resistance to oxidative stress. Products of the
unc-13 gene regulate neurotransmitter release from all neurons in C. elegans and defects in this gene result in decreased abundance of neurotransmitters in synapses and paralysis. When wild type C. elegans are exposed to oxidative stress, there is a delay in the development of worms to adulthood. Following exposure of
unc-13 mutants to the chemical paraquat, which induces oxidative stress, we found that
unc-13 worms develop to adulthood later than wild type. Using strains with GFP labeled neurons, we examined the number of GABAergic, dopaminergic, and serotonergic neurons in worms with a normal functioning nervous system and with a mutation in
unc-13 following exposure to paraquat. There was a decrease in the number of GFP labeled neurons and more neurons were missing in the
unc-13 strain. These findings suggest that
unc-13 mutants with decreased neurotransmitter release have increased sensitivity to oxidative stress. We plan to perform experiments to determine whether the GFP labeled neurons are undergoing apoptosis or necrosis.