Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity

Abstract

Study objectives: This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats.

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 h) sleep-deprived adult male Wistar 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 by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction.

Measurement and results: The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, shortterm memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP.

Conclusions: The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats.

Figure 1

Effect of chronic caffeine treatment on sleep deprivation-impaired learning and short-term memory tests in the radial arm water maze. (A) Sleep-deprived rats showed significant impairment of learning in trials number 7, 11, and 12 compared to rats in control, wide platform, caffeine, and caffeine/sleep deprivation. Additionally, short-term memory was markedly impaired in sleep-deprived rats, but was normal in caffeine-treated rats. (B) The average number of errors made by each of the 5 groups in short-term memory test, 30 min after trial # 12. Chronic caffeine treatment before sleep deprivation prevented learning and short-term memory impairment. Each point is the mean ± SEM of 10 to 12 rats. *Indicates significant difference from other groups (P < 0.01).

Figure 2

Early-phase long-term potentiation (E-LTP) of area CA1 evoked by high-frequency stimulation (HFS) at time zero, measured as increase in the slope of fEPSP and pSpike amplitude. (A) Chronic caffeine treatment prevents sleep deprivation-induced E-LTP impairment in the CA1 area. Sleep deprived rats exhibit markedly impaired slope of fEPSP, but chronic caffeine treatment prevents fEPSP slope impairment. (B) Chronic caffeine treatment before sleep deprivation prevents the decrease in pSpike amplitude. Each point is the mean ± SEM of 4-6 rats. All points between (*) are significantly different from other groups (P < 0.05). Inset is a representative experiment; calibrations, 5 mV/5 ms, apply to all traces.

Figure 3

Effect of chronic caffeine treatment and/or sleep deprivation on protein levels of P-CaMKII (A) and total CaMKII (B) 1 h after the induction of E-LTP, measured in the septal side of area CA1 and expressed as a ratio to the temporal side. “S” refers to stimulated groups. Each point is the mean ± SEM of 4-6 rats. *Indicates significant difference from unstimulated control group (P < 0.05).

Figure 4

Effect of chronic caffeine treatment and/or sleep deprivation on the protein levels of calcineurin (A) and BDNF (B) 1 h after the induction of E-LTP; measured in the septal CA1 area and expressed as a ratio to the temporal side. “S” refers to the stimulated group. Each point is the mean ± SEM of 4-6 rats. *Indicates significant difference from unstimulated control group (P < 0.05).