Caffeine-augmented exercise as a pretreatment for locomotor and balance impairments induced by REM sleep deprivation in rats

Sleep deprivation (SD) is a common problem that can lead to various neurological disorders. This study was carried out to examine how SD impacts locomotor performance and coordination in rats. Moreover, we aimed to investigate the potential synergistic benefits of caffeine supplementation coupled with treadmill exercise in mitigating any locomotor disorders induced by SD. Male rats were assigned to five groups: control, SD, SD + caffeine, SD + exercise, SD + caffeine + exercise. After 5 weeks of receiving caffeine supplementation (30 mg/kg) and/or treadmill exercise, the rats underwent 72 h of REM-SD, followed by behavioral tests. Subsequently, various analyses, including electrophysiology recordings, oxidative stress levels, neuroinflammation markers, apoptosis indicator, and histological changes were evaluated in the striatum and cerebellum. REM-SD significantly impaired motor and balance function, decreased neuronal activity, and increased oxidative stress, inflammatory, and apoptotic markers in the striatum and cerebellum. The study also found that REM-SD led to induce histopathological changes in these brain regions. Importantly, the administration of caffeine or regular exercise helped mitigate these adverse effects of REM-SD on motor, neuronal, molecular, and histological measures. Moreover, the combination of caffeine and exercise proved particularly effective, as it not only improved the motor and neuronal deficits, but also reduced the oxidative stress, inflammatory and apoptotic factors. The findings suggest that caffeine and exercise synergistically mitigate REM-SD-induced locomotor and neuronal deficits, particularly in locomotion and balance-related brain regions, potentially through reducing oxidative stress, inflammation, and apoptosis.