Thesis

The effects of alpha-synuclein on behavioral dysfunctionin the parkinson’s disease model drosophila melanogaste

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Research has identified several factors that play an important role in PD, and one of the factors is protein called α-synuclein.Overexpression of A30P or A53T promotes the formation of toxic filamentous inclusions in neurons that mediate motor output, resulting in movement deficits. The present study involved using Drosophila melanogasterto examine the behavioral dysfunction associated with α-synuclein linked to PD. The specific aim of this study was to develop an obstacle avoidance behavioral assay to quantify motor control and movement planning deficits in flies. Flies were genetically altered to carry A30P or A53T protein in specific brain regions known to be associated with sensory integration and locomotor abilities in insectsand their behavior assessed at different ages. Our data suggest that Drosophila expressing α-synuclein exhibit significantly different locomotor responses in speed and distance of negotiating an obstacle, with the greatest deficitsin central complex mutants.Moreover, aged mutant flies had lower success rate in negotiating the obstacle than young flies. These findings suggest that flies expressing α-synuclein may have issues with coordinating and executing fine control of movement in the obstacle avoidance activity. Therefore, this study can provide new insight into our understanding of the potential effects of α-synuclein in PD.

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