Bidirectional Effects of Sleep Deprivation Associated with Parkinson's Disease on Behavior, Oxidative Stress, and Energy Metabolism in Male and Female Rats.

Parkinson's disease (PD) is a progressive neurodegenerative disorder. Sleep deprivation (SD) can exacerbate PD symptoms, while neurodegeneration itself may impair sleep architecture, suggesting a bidirectional interaction between these conditions. This study aimed to investigate the interplay between PD and SD, evaluating their effects on behavioral parameters, mitochondrial activity, and oxidative stress markers. Male and female Wistar rats were allocated to control, SD, PD, and combined exposure groups. PD was induced by 6-hydroxydopamine, and SD by the single-platform method. Behavioral (locomotion, anhedonia) and biochemical assays were performed to assess mitochondrial function and oxidative stress. The results demonstrated that both PD and SD markedly influenced behavioral, mitochondrial, and oxidative parameters, with their effects distinctly modulated by biological sex and the sequence of exposure. PD alone enhanced mitochondrial enzymatic activity and oxidative stress, whereas SD exerted variable effects contingent upon exposure order and sex, differentially shaping behavioral outcomes and redox homeostasis. Notably, specific brain regions exhibited increased susceptibility to the combined challenges of PD and SD, suggesting synergistic neurotoxic interactions. Collectively, these findings reinforce the bidirectional relationship between PD and SD, providing novel insights into the mechanistic interplay linking sleep disruption and neurodegeneration. The identified sex-dependent and region-specific responses underscore the need for personalized therapeutic strategies and emphasize the critical role of sleep quality and other lifestyle factors in the clinical management of PD.