Evaluating the Role of CAMP in Sleep Deprivation

Abstract

Sleep deprivation is a condition of disrupted sleep cycle, it happens when an individual does not get enough sleep necessary for the individual to wake up alert enough during the day. It can be acute or chronic. Some of the causes of sleep deprivation are imposed on the individual as the nature of his/her occupation and working schedule, health conditions, use of some drugs and insomnia. Other causes are related to habits or individual responses as excessive alcohol consumption, personal obligations and emotional stress. cAMP is an important secondary messenger and it regulates a lot of functions in the human body. Rolipram is a phosphodiesterase-4 inhibitor and should prevent the hydrolysis of cAMP. On the other hand the action of chlorogenic acid is to activate calcineurin which inactivates the DARPP-32 thus allowing the dephosphorylation of protein kinase A and reversing the action of cAMP. The aim of this study is to investigate a different mechanism by which cAMP affects sleep deprivation and the effects of its elevation on memory and the learning abilities of sleep deprived mice using rolipram and chlorogenic acid. Induction of sleep deprivation test used in this study by flower pot method dividing the mice into four groups each group consists of six mice. Mice injected with the corresponding treatment and their learning memory tested with Morris water maze. Hippocampus screening is used for the assay of cAMP and Nrf-2 using ELISA. GSK3β, CREB and PKA levels are measured by Western Blot technique. The results showed that the rolipram inhibits the degradation of cAMP that activates the PKA pathway the level of GSK3-beta, NFR2 and the CREB increased. In conclusion, activation of cAMP leads to improvement of memory, increase of cognition abilities and decrease in inflammation and oxidative stress. On the other hand cholorgenic acid has opposing mechanism against rolipram which leads to decrease in the levels of GSK3-b, NFR2 and CREB.