Metformin reduces seizure-like activity in the Bang-sensitive paralytic mutants easily-shocked and technical knockout. Daniel R. Kuebler, Bryan Stone. Dept Biology, Franciscan University, Steubenville, OH.

   The Bang-sensitive (BS) paralytic mutants are susceptible to seizure-like activity (SLA) following a variety of insults. The SLA that occurs in the BS mutants is characterized by violent uncoordinated contractions of the legs, wings and abdomen that cause the flies to spin and move violently. These mutants have proven to be a valuable model for investigating the etiology of seizure disorders as they have been used to identify genetic and pharmacological suppressors of seizure susceptibility. In addition, previous work with the BS mutants has identified an association between alterations in metabolism and the amount and intensity of SLA. We have found that the drug metformin, which is used to treat type II diabetes, reduces SLA intensity and duration in two of the BS mutants easily-shocked (eas) and technical knockout (tko). Metformin is known to decrease oxidative phosphorylation and increase glycolysis in mammalian cells. We have examined its effect on metabolism in these BS mutants as well as its effect on glycolytic gene expression to see if these correlate with its ability to suppress SLA.