Walking deficits and centrophobism in an α-synuclein fly model of Parkinson's disease

Parkinson's disease (PD) is a movement neurodegenerative disorder, characterized by bradykinesia, rigidity and tremor, constituting difficulties in walking and abnormal gait. Previous research shows that Drosophila expressing human α-synuclein A30P (A30P) develop deficits in geotaxis climbing; however, geotaxis climbing is a different movement modality from walking. Whether A30P flies would exhibit abnormal walking in a horizontal plane, a measure more relevant to PD, is not known. In this study, we characterized A30P fly walking using a high-speed camera and an automatic behavior tracking system. We found that old but not young A30P flies exhibited walking abnormalities, specifically decreased total moving distance, distance per movement, velocity, angular velocity and others, compared with old control flies. Those features match the definition of bradykinesia. Multivariate analysis further suggested a synergistic effect of aging and A30P, resulting in a distinct pattern of walking deficits, as seen in aged A30P flies. Psychiatric problems are common in PD patients with anxiety affecting 40-69% of patients. Central avoidance is one assessment of anxiety in various animal models. We found old but not young A30P flies exhibited increased centrophobism, suggesting possible elevated anxiety. Here, we report the first quantitative measures of walking qualities in a PD fly model and propose an alternative behavior paradigm for evaluating motor functions apart from climbing assay.