Effects of VPA on Mutated C. elegans

Valproic acid (VPA) is a generalized drug used to alleviate a broad range of conditions in humans such as bipolar disorders as well as Parkinson’s disease, epilepsy, and other neuromuscular diseases. The use of VPA in treatment of such diseases is due to its properties as a neurotransmitter inhibitor. In studies involving the N2 strain (wild type) of C. elegans, VPA has been shown to increase their lifespans through the regulation of insulin/IGF-1 growth factor signaling pathways. However, in humans, VPA can cause serious side effects, such as liver problems, bleeding, and a reduction in blood platelet count. In addition, VPA can decrease diacylglycerol (DAG) production and inhibit IP3 signaling in C. elegans, which results in the suppression of egg laying; the IP3 signaling pathway involves the release of calcium ions from endoplasmic reticulum into the intercellular matrix. In our study, we want to create a mutant of C. elegans resistant to these egg-laying inhibitory effects that VPA causes. The mutation in the experiment was induced by ethyl methanesulfonate (EMS). The mutants C. elegans were then bred and screened for their ability to reproduce when exposed to VPA. This procedure was performed and repeated until a generation of consistently VPA-resistant offspring was evident. The results of the project have positive implications for the future of VPAss use. If the induced mutations can be used to offset some of the negative side effects of VPA in C. elegans, then it may be worth researching possible ways to reduce the negative side effects that VPA causes in humans.