Evaluation of foxO modulation in modelling Parkinson Disease in Drosophila melanogaster

Chavoshi Jolfaei, Mahin S. (2014) Evaluation of foxO modulation in modelling Parkinson Disease in Drosophila melanogaster. Masters thesis, Memorial University of Newfoundland.

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Abstract

Symptoms of Parkinson Disease (PD), the second most common neurodegenerative disease, emerge due to degeneration of dopaminergic neurons. Approximately 10% of PD is familial with a number of genes that have been recognized to play a role. In 2012, a genome wide study revealed a role for the foxO transcription factor in PD. To more fully understand human diseases, model organisms such as Drosophila melanogaster are widely used. In the present study, I have attempted to model Parkinson Disease in Drosophila by foxO modulation using RNAi transgenes. To achieve this goal, I conducted longevity assays and locomotion measurements along with supportive experiments that target expression in the developing eye. Results suggest that under certain conditions, slight elevation of foxO by down-regulation of one of foxO’s inhibitors, the kinase minibrain (mnb), can model PD in flies. Results are presented here showing that expression of mnb-RNAi (and predicted subsequent slight elevation of foxO) in dopaminergic neurons results in significant loss of climbing ability: the defining feature of PD models in fruit flies. Other results suggest that slight decrease of foxO by foxO-RNAi decreases life span significantly when expressed under the control of TH-Gal4( Tyrosine Hydroxylase-Gal4) . In addition, results show that GFP-RNAi expression under the control of TH-Gal4 reduces life span significantly.

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