Thesis
French
ID: <
10670/1.tgy698>
Abstract
Long-term disruption of circadian clocks, as occurs often in our "24/7 societies", can be detrimental. These clocks control self-sustained biological rhythms with ~24h periodicity and synchronize to the daily light-dark cycle. Clock disruption may impact normal brain aging as well as Parkinson disease (PD) pathogenesis: PD patients frequently exhibit non-motor symptoms including sleep and/or circadian rhythm disruptions that occur before motor or cognitive deficits, and decrease quality of life. The objective of this PhD work was thus to explore the impacts of circadian disruptions on age-related functional decline, both during normal aging and in a fly model of PD-like conditions using well established Drosophila models. Our results confirmed the negative impact of circadian arrhythmia on longevity and revealed that inactivation of a specific circadian gene, Clock (Clk), increases brain oxidative stress levels and accelerates locomotor decline during aging. The latter effect could be associated with Clk function in the clock neurons that drive circadian rest-activity rhythms in constant darkness, and their connections with a specific cluster of dopaminergic neurons. We also observed that chronic jet lag led to an accelerated age-related locomotor decline that could be rescued by adapting the light-dark to the flies’ endogenous period. Finally, our work demonstrated the negative impact of environmentally imposed circadian arrhythmia on age-related locomotor decline in a fly model of PD.