The Role of Oxidative Stress in a Drosophila Model of Fetal Alcohol Syndrome

Fetal alcohol syndrome (FAS) is a spectrum disorder affecting individuals exposed to ethanol during gestation and often results in developmental delays, decreased survival rates, growth and development defects, behavioral changes, and altered adult responses to ethanol; it is also the leading cause of non-genetic mental retardation. Previous studies have shown Drosophila melanogaster larvae exposed to ethanol-treated food model these phenotypes. The purpose of this study is to determine whether oxidative stress is playing a role in these ethanol-induced phenotypes. We hypothesize that artificially inducing oxidative stress should phenocopy some or all of the FAS symptoms, while alleviating oxidative stress should correspondingly ameliorate the phenotypes. Both pharmacological and genetic manipulations were utilized to induce or alleviate oxidative stress, either alone, or in conjunction with ethanol exposure. To date, using transgenic constructs to pan-neuronally upregulate the antioxidant enzyme superoxide dismutase resulted in increased resistance to ethanol-induced lethality, but no change in developmental delay. However, developmental exposure to hydrogen peroxide has been found to phenocopy the delay and decreased survival phenotypes, as well as preliminary data indicating that some of the adult responses to ethanol may be affected. Additionally, biochemical markers of oxidative stress are being assessed in ethanol-reared larvae via western blot, and preliminary data indicate that antioxidant gene products are upregulated. Collectively, these data implicate oxidative stress in ethanol-induced phenotypes, specifically in relationship to the decreased survival and developmental delays. Future work will include more genetic screening and western blots for other markers of oxidative stress.