Parkinson's Disease-Associated Genetic Alterations Disrupt Behavior and Diurnal Activity in Drosophila melanogaster

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons, resulting in motor dysfunction and a variety of non-motor symptoms. Multiple genetic alterations, including increased α-synuclein expression and loss-of-function of parkin, PINK1, and DJ-1, have been associated with PD pathogenesis; however, their effects on stress tolerance, motor behavior, and daily activity remain incompletely understood. This study investigated the effects of PD-associated genetic alterations on stress tolerance, motor behavior, and diurnal activity in Drosophila melanogaster. Four Drosophila lines representing PARK1 (SNCA/α-synuclein; elav-GAL4>UAS-hSNCA), PARK2 (PRKN/parkin; parkinⁿᵘˡˡ), PARK6 (PINK1; PINK1ᴮ⁹), and PARK7 (DJ-1; DJ-1βΔ⁹³) were evaluated using assays of starvation survival, larval vertical migration, adult negative geotaxis, jumping activity, and locomotor activity under a 12h light:12h dark cycle. Starvation stress tolerance differed among PD-associated fly lines in males and females separately. All PD-associated fly lines exhibited impaired larval vertical migration, whereas adult negative geotaxis and jumping behavior showed genotype-dependent patterns, with no significant genotype × sex interaction. Activity monitoring revealed disruptions in daily locomotor activity, with visually observed alterations in morning and evening activity patterns. Daily activity patterns also showed clear sex-specific differences. These findings show that PD-associated genetic alterations affect stress tolerance, locomotor behavior, and diurnal activity in D. melanogaster, with the nature of these effects varying by genotype, sex, and behavioral phenotype. The findings further highlight the importance of considering sex as a biological variable in PD research. Further studies are needed to define the molecular mechanisms underlying these behavioral and diurnal alterations.