Evidence demonstrates that sleep deprivation (SD) impairs memory, cognitive function, and mood state. The disruption of the circadian rhythm induced by SD during the REM phase (REM-SD) leads to oxidative stress, neuroinflammation, and apoptosis proportional to the duration of the deprivation, but the underlying mechanisms remain largely unknown. Caffeine, which has neuroprotective effects, could prove beneficial in mitigating the effects of SD. In the present study, using the MMPM model, we investigate the neuroprotective effects of caffeine in rats subjected to REM-SD and elucidate the underlying mechanisms. Rats received caffeine (0.3 g/l) during 5 weeks of REM-SD. We then assessed affective and cognitive functions using behavioral tests. We evaluated blood levels of hs-CRP and CORT, as well as AchE, LDH activity, and oxidative stress markers in the HP, PFC, and HYP. Therefore, histological staining of these brain structures was examined. Caffeine treatment significantly improved memory and cognitive function in rats subjected to REM-SD. The study also showed that caffeine reduces hs-CRP, attenuates SD-induced HPA axis hyperactivation, decreases markers of oxidative stress, and enhances antioxidant defenses. Importantly, caffeine treatment modulates the cholinergic system, prevents neuronal lysis, and preserves neuronal density and architecture. The findings suggest that caffeine exerts neuroprotective, anti-inflammatory, antioxidant, and cytoprotective effects by preserving neuronal architecture against the effects of SD.
