The Role of Oxidative Stress in a Drosophila Model of Fetal Alcohol Syndrome. Theresa A. Logan-Garbisch¹, Kiara Y. Amaro-Rivera^1,2, Audrey A. Ford¹, David Do^1,3, Hilal J. Jarar¹, Melissa K. Ruiz¹, Omar Fateen¹, Rachael French¹. 1) Biological Sciences, San José State University, San José, CA; 2) Industrial Biotechnology Department, University of Puerto Rico-Mayagüez, Yaguez, Mayagüez, Puerto Rico; 3) Computer Science, San José State University, San José, CA.

   Fetal alcohol syndrome (FAS) is a spectrum disorder affecting individuals exposed to ethanol during gestation and often results in developmental delays and decreased survival rates; 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. We hypothesize that ethanol and oxidative stress are acting in the same pathway and therefore predict that 1) oxidative stress will phenocopy FAS symptoms; 2) increased oxidative stress will increase sensitivity to ethanol exposure; 3) alleviated oxidative stress will ameliorate the phenotypes, and 4) threshold doses of ethanol and peroxide will act synergistically. Both pharmacological and genetic manipulations were utilized to induce or alleviate oxidative stress. To date, developmental exposure to hydrogen peroxide has been found to phenocopy the delay and decreased survival phenotypes. Transgenic constructs which pan-neuronally upregulate the antioxidant enzyme superoxide dismutase (sod) resulted in increased resistance to ethanol-induced lethality. Correspondingly, pan-neuronal downregulation of sod resulted in increased lethality. Moreover, flies exposed to combined threshold doses of peroxide and ethanol show increased developmental delays and decreased survival when compared to conditional controls. In addition, microarray data indicate that some markers of oxidative stress are significantly altered in larvae reared in ethanol relative to unexposed larvae. Collectively, these data implicate oxidative stress in ethanol-induced phenotypes, specifically in relationship to the decreased survival and developmental delay. Future work includes looking for biochemical markers of oxidative stress in ethanol-reared larvae via western blot as well as immunohistochemistry assays.