A Novel, Sensitive Assay for Behavioral Defects in Parkinson's Disease Model Drosophila

Abstract

Parkinson's disease is a common neurodegenerative disorder with the pathology of α-synuclein aggregation in Lewy bodies. Currently, there is no available therapy that arrests the progression of the disease. Therefore, the need of animal models to follow α-synuclein aggregation is crucial. Drosophila melanogaster has been researched extensively as a good genetic model for the disease, with a cognitive phenotype of defective climbing ability. The assay for climbing ability has been demonstrated as an effective tool for screening new therapeutic agents for Parkinson's disease. However, due to the assay's many limitations, there is a clear need to develop a better behavioral test. Courtship, a stereotyped, ritualized behavior of Drosophila, involves complex motor and sensory functions in both sexes, which are controlled by large number of neurons; hence, behavior observed during courtship should be sensitive to disease processes in the nervous system. We used a series of traits commonly observed in courtship and an additional behavioral trait—nonsexual encounters—and analyzed them using a data mining tool. We found defective behavior of the Parkinson's model male flies that were tested with virgin females, visible at a much younger age than the climbing defects. We conclude that this is an improved behavioral assay for Parkinson's model flies.