INTRODUCTION: Parkinson’s disease (PD) is one of the most common age-related neurodegenerative disorders, connected with the loss of dopaminergic neurons in the substantia nigra. It’s early-onset form is associated with mutation in the park gene. PARKIN protein initiates process of ubiquitination and degradation of damaged mitochondria on the pathway called mitophagy, a mechanism which is conserved across species.

AIM(S): One of the earliest signs of the disease are sleep disturbances, which appear before any motor symptoms. In this study, we used fruit fly, Drosophila melanogaster to investigate the effect of park mutation on clock neurons. The main oscillator is located in the sLNv neurons, which specifically express Pigment Dispersing Factor (PDF) and project their axons to the dorsal part of the brain. These terminals show circadian plasticity, being most branched in the morning and least at the evening, which provides different synaptic partners across the day. This mechanism regulates many processes, including the sleep and activity pattern.

METHOD(S): To examine how mitophagy disruption affects clock neurons, we used flies with a park mutation and with park silenced in sLNv and dopaminergic neurons. We analyzed activity and sleep profiles to check whether PD model flies have circadian disruption. We collected heads at two time points, at the beginning of the day and of the night and using anti-PDF immunostaining we visualized terminals to analyze their complexity using Sholl method.

RESULTS: The obtained results were very similar across all three experimental genotypes. They showed lower amplitude of activity during the morning and evening peak. Moreover, we observed disrupted rhythmicity in branching complexity.

CONCLUSIONS: Our results suggests that mitophagy disruption causes clock dysfunction, however the mechanism is more complex. It is possible that increased oxidative stress directly in clock neurons, or in neighboring cells desynchronizes sLNv physiology and in effect affects activity and sleep pattern.

FINANCIAL SUPPORT: NCN grant no. UMO-2022/46/E/NZ3/00095