Effect of Ang II Receptor Inhibition on GSK-3β/CREB/BDNF Signalling in REM Sleep Deprivation-Induced Memory Impairment.
📄 Abstract
REM (rapid eye movement) sleep deprivation causes serious impairments in hippocampus-dependent learning and memory. This study examined whether the angiotensin II receptor blocker telmisartan, given at two different doses, could reduce cognitive deficits and affect molecular pathways related to chronic REM sleep deprivation. Thirty-two male Wistar-Albino rats (200-280 g, 3 months old) were randomly divided into four groups (n = 8): control, sleep deprivation (SD), telmisartan-treated SD groups at 1 mg/kg (SD+Tel1) and 3 mg/kg (SD+Tel3). Chronic REM sleep deprivation was induced for 21 days using the modified multiple platform (MMP) method. Telmisartan or distilled water was administered orally once daily. Cognitive performance was tested in the Morris water maze, assessing escape latency and time spent in the target quadrant. After behavioral tests, hippocampal and prefrontal cortex samples were analyzed for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), glycogen synthase kinase-3 beta (GSK-3β), monocarboxylate transporter 2 (MCT2), and lactate dehydrogenase (LDH) levels, while plasma samples were analyzed for corticosterone (CORT) levels. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitrate, and glycogen were also measured. Sleep-deprived rats showed impaired learning and memory with longer escape latency and reduced time spent of target quadrant. Telmisartan-treated SD groups demonstrated significantly improved cognitive performance, increased BDNF and CREB expression, decreased GSK-3β levels, and balanced oxidative stress markers. In conclusion, telmisartan protected against cognitive and biochemical damage caused by chronic REM sleep deprivation, likely through modulation of GSK-3β/CREB/BDNF signaling and reduction of oxidative stress.