Caffeine and Exercise: A Dual Approach to Combat Cognitive Decline Induced by REM Sleep Deprivation.

Sleep deprivation (SD) is known to impair memory and cognitive functions often linked to heightened oxidative stress and neuroinflammation. While caffeine and exercise individually offer neuroprotective effects, the combined influence of these interventions on preserving cognitive function and reducing hippocampal damage during REM-SD has yet to be fully explored. This study investigates the synergistic potential of caffeine and exercise in mitigating these neurological damages induced by REM-SD. Male Wistar rats were divided into five groups: control, SD, caffeine + SD, exercise + SD, and caffeine + exercise + SD. The rats received caffeine (30 mg/kg, p.o) and underwent a treadmill exercise regimen, running 5 days a week for 4 weeks. Following this, they were placed in a REM-SD apparatus for 72 h. We evaluated the cognitive functions of the animals using standard behavioral tests. In addition, we assessed BBB permeability, brain water content (BWC), oxidative-antioxidative status, inflammatory/anti-inflammatory conditions, and apoptotic and neurotrophic indices in the hippocampus of REM-SD rats. Our findings indicate that the combination of caffeine and exercise significantly enhanced cognitive functions in REM-SD rats. This combination also reduced BBB permeability and BWC, alleviated oxidative stress, lowered inflammatory and apoptotic indices, and increased neurotrophic gene expression in the hippocampus of REM-SD rats. This study highlights the protective effects of caffeine and exercise on cognitive function and BBB integrity, likely through the enhancement of antioxidant and anti-inflammatory indices in the hippocampus, as well as their anti-apoptotic and neurotrophic effects in REM-SD rats.