Determining the tissue basis of nicotine rescue in the Drosophila Parkinsons Disease model. David O. Meyer¹, Lori M. Buhlman¹, Gerald B. Call². 1) Dept. of Biomedical Sciences, Midwestern University, Glendale, AZ; 2) Dept. of Pharmacology, Midwestern University, Glendale, AZ.

   The Drosophila Parkinsons Disease (PD) model based on homozygous loss of function of the parkin gene has been shown to have both flight muscle degeneration and dopaminergic neuronal loss in the brain. Our previous data also indicates that flies heterozygous for the park²⁵ null allele also experience motor function defects, olfaction loss and decreased lifespan. Interestingly, administration of nicotine to these flies in their food improved or rescued all of the observed deficits. This study was initiated to determine the mechanism of this rescue by histological and genetic methods. The first method consists of histologically analyzing the indirect flight muscle and dopaminergic neurons in the brain to determine if the morphology or numbers of these tissues are affected by nicotine treatment. Initial results indicate that nicotine does not affect neuron numbers in 20-day-old park²⁵ heterozygotes, nicotine = 12.62 neurons/cluster (n=37) vs. no nicotine = 12.92 neurons/cluster (n=26). Further analysis, including muscle morphology will be presented at the meeting. In addition to histological analysis, a genetic mechanism using RNAi to knock down Parkin in a tissue specific manner will help us determine the site of nicotine rescue. We are currently determining if using Actin-Gal4 to drive expression of UAS-park RNAi can phenocopy the park²⁵ flies. These experiments are underway and will be presented at the meeting. These results will help identify where nicotine is rescuing the phenotypes observed in this model in an effort to help understand PD better.