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

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.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Pharmacology

Grantor

University of Houston

Year dc:date.issued

2010

Author dc:creator

• Alhaider, Ibrahim

Advisor dc:contributor.advisor

• Alkadhi, Karim A.

Committee members dc:contributor.committeemember

• Lau, Yuen-Sum
• Hussain, Tahir
• Leasure, J. Leigh
• Aleisa, Abdulaziz M.

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

Statement dc:rights

• The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10657/ETD-UH-2010-05-31

OAI identifier oai:identifier

oai:uh-ir.tdl.org:10657/ETD-UH-2010-05-31