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

Abstract

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.

Glial α‐synuclein promotes neurodegeneration characterized by a distinct transcriptional program in vivo

“…Motor symptoms are the defining clinical feature of parkinsonism, and motor dysfunction has been previously demonstrated in Drosophila models of Parkinson's disease in the form of impaired climbing (Feany & Bender, ; Ordonez et al, ), walking (Chen, Wilburn, Hao, & Tully, ; Pokrzywa et al, ), and proboscis extension (Cording et al, ). Using our model of glial α‐synucleinopathy, we compared locomotor behavior in control flies to flies expressing α‐synuclein in glia, neurons, or both cell types.…”

“…3.2 | Glial α-synuclein impairs locomotion (Feany & Bender, 2000;Ordonez et al, 2018), walking (Chen, Wilburn, Hao, & Tully, 2014;Pokrzywa et al, 2017), and proboscis extension (Cording et al, 2017). Using our model of glial α-synucleinopathy, we compared locomotor behavior in control flies to flies expressing α-synuclein in glia, neurons, or both cell types.…”

Cross-talk between amyloidogenic proteins in type-2 diabetes and Parkinson’s disease

“…It is characterized by widespread degeneration of subcortical structures of the brain, especially dopaminergic neurons in the substantia nigra. These changes are coupled with bradykinesia, rigidity, and tremor, resulting in difficulties in walking and abnormal gait in patients (1). The assembly process of the intrinsically unstructured 140-residue protein α-synuclein (aS) into amyloid fibers has been linked to the molecular basis of PD.…”

“Plasma Membrane Calcium Atpase downregulation in dopaminergic neurons alters cellular physiology and behavior in Drosophila melanogaster”

“…No difference was observed in previous times. To evaluate the general walking status of the PMCA RNAi expressing flies we additionally used the open field assay similar to [14]. We measured walking parameters including total distance walked and maximum time of detention.…”

“…Data from 5 technical replicates from each of 3 independent biological experiments per genotype were analyzed. Open field assay with video tracking A panel of 8 arenas of 3.5 cm in diameter was used, allowing a simultaneous recording of 8 flies similar to [14] using a Logitech camera. Arenas were placed above an array of white LEDs.…”