THE PROTECTIVE EFFECTS OF CHRONIC CAFFEINE TREATMENT ON THE COGNITIVE FUNCTION AND SYNAPTIC PLASTICITY IN ACUTE SLEEP DEPRIVATION

Date

2010-05

Journal Title

Journal ISSN

Volume Title

Publisher

Abstract

Study objectives: Accumulating evidence has shown that caffeine and sleep deprivation have opposing effects on learning and memory; therefore, this study was undertaken to provide a detailed account of the effect of chronic, low-dose caffeine treatment on the deleterious effects of sleep loss on hippocampus-dependent learning and memory. Experimental design: We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/l in drinking water) on memory impairment in acutely (24 hr) sleep-deprived rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied using three approaches: learning and memory performance in the radial arm water maze task; electrophysiological recordings in the Cornu Ammonis (CA1) and dentate gyrus (DG) regions of the hippocampus; and western blot analysis to measure the levels of memory- and synaptic plasticity-related signaling molecules. Results: Our results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, short-term memory and early phase- long-term potentiation (E-LTP) of the CA1 and DG areas in the sleep-deprived rats. In correlation, caffeine treatment prevented a sleep deprivation-associated decrease in the basal levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) and brain-derived neurotrophic factor (BDNF). In addition, caffeine treatment of sleep-deprived rats increased the levels of P-CaMKII during the expression of E-LTP. The results also showed that chronic caffeine treatment prevented the impairment of long-term memory and late phase-LTP (L-LTP) in the CA1 and DG regions of the sleep-deprived rats. Additionally, caffeine treatment prevented a sleep deprivation-associated decrease in the basal levels of the phosphorylated cAMP response element binding protein (P-CREB) as well as total CREB. Treating sleep-deprived rats chronically with caffeine enables multiple high frequency stimulation to increase the levels of P-CREB during L-LTP expression. Conclusions: The results suggest that long-term use of a low dose of caffeine protects against the harmful changes in the basal levels of P-CaMKII, P-CREB and BDNF associated with sleep deprivation and as a result contributes to the revival of hippocampus-dependent learning and memory as well as LTP in the CA1 and DG regions.

Description

Keywords

Caffeine, Sleep deprivation, Memory, Hippocampus, Long-term potentiation, Spatial memory, CREB, CaMKII, CA1 area, DG area

Citation