Identifying the molecular mechanism of nicotine-mediated rescue in a fly model of Parkinson's disease. Jared Techau¹, Gerald B. Call², Lori M. Buhlman¹. 1) Biomedical Sciences, Midwestern University, Glendale, AZ; 2) Dept. of Pharmacology, Midwestern University, Glendale, AZ.

   Parkinsons disease (PD) is characterized by the death of dopaminergic neurons in the substantia nigra pars compacta, which leads to motor and non-motor dysfunctions. It exists in both sporadic and familial forms, where prior studies have shown that nicotine exhibits neuroprotective effects in decreasing incidence of sporadic PD and delaying onset of motor symptoms (Quik et al., 2009). We have previously demonstrated that nicotine can rescue a familial model of PD in Drosophila melanogaster that have a heterozygous parkin loss-of-function mutation through behavioral assays such as climbing, flight, and olfaction as well as in lifespan. We sought to determine whether this protective effect of nicotine was mediated through activation of the Drosophila nicotinic acetylcholine receptor (DnAChR). A nonselective nAChR antagonist, mecamylamine, has been administered to determine if the neuroprotective effects of nicotine are antagonized or diminished in the same behavioral assays in the park²⁵ heterozygotes. Our initial results indicate that nicotine may be eliciting its protective effects by acting through a DnAChR-independent manner in both climbing and flight assays. This data might indicate that nicotine is producing its protective effect by directly affecting other cellular targets directly, (e.g., mitochondria) in these flies.