Dopamine Kinetics in a Drosophila Model of Parkinson Disease 998 views

Parkinson disease (PD) is a neurodegenerative movement disorder, with motor symptoms caused by the death of dopaminergic cells in the central nervous system. RING finger protein 11 (RNF11) has been identified in vulnerable neurons of the substantia nigra in Parkinson disease patients, and localized to the Lewy bodies of humans with idiopathic disease. In order to study the effects of RNF11 on dopamine neurotransmission, it was necessary to improve the techniques to detect dopamine at a millisecond time scale in Drosophila. Pulsed light stimulations were used alongside Michaelis-Menten modeling to characterize release and uptake of dopamine upon optogenetic stimulation. In order to avoid the electrochemical defect at the switching potential caused by blue light, a red light activated channelrhodopsin, CsChrimson, was characterized and used to measure from a novel region of the central nervous system, the protocerebrum. Using these new techniques, we tested the hypothesis that RNF11 modulates dopamine neurotransmission in Drosophila larvae. We identified RNF11 as a protein that may be a target for timely intervention and pharmacological prevention of Parkinson disease progression.

PHD (Doctor of Philosophy)

Dopamine, Drosophila, Parkinson Disease

English

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2016-07-21