The Expression Of Cannabinoid Receptor 1 MRNA After Rapid Eye Movement Sleep Deprivation In Rat Hippocampus And Its Contribution To Epilepsy

BackgroundSleep has two different stages,one is slow wave sleep (SWS) the other is rapid eye movements sleep(REM). REM sleep is good for the development of the neurons. Sleep deprivation(SD) can cause nervouse,tiresome, immune- disorder and epilepsy.The research of sleep deprivation ; cannabinoid receptor 1 and epilepsy has not been discussed nowday. In this study we observed the expression of cannabinoid receptor 1 after rapid eye movement sleep deprivation in rat hippocampus and its contribution to epilepsy. Our goal was to determine the effect of sleep deprivation on neurons and how CB-1 receptor play an important role in epilepsy.Objects and MethodsTotally 65 Sprague-Dawley male rats weighing 220-250g were involved in the experiment and divided randomly into two groups,as epilepsic group and unepilepsicgroup.The rats of unepilepsic group were divided randomly as cage control(CC),tank control(TC)and the sleep deprivation group(SD).The SD and TC group animals were sacrificed at the end of ld,3d,5d sleep deprivation periods respectively.The rats of epilepsic group were also divided randomly as tank control(TC)and the sleep deprivation group(SD).The modified multiple plateform methods(MMPM)were established for the rapid eye movement(REM)sleep deprivation. CB-1 receptor mRNA were measured by using reverse transcription-polymerase chain reaction(RT-PCR). The different stage of ultrostructure were observed through electro-microscope. Using pentetrazole(PTZ) to induce convulsion and observe the expression of CB-1 receptor after seizure.The data was presented as means and standard deviations (x ± s) .Independent samples T-test was performed among groups.Multiple linear regression analysis was performed in epilepsic groups.ResultsAfter 1 day sleep deprivation the rats became irritating.Three days later the phenomenon was more serious.At the end of 5 days the rats calmed down. Neurons apoptosis were found in the SD3d and SD5d groups through electro-microscope.The SD1d group displayed increased expression of CB-1 receptor as compared with the TC1d group(P<0.05) while the SD3d group displayed minimum expression. The SD5d group did not experience significant changes as compared with the TC5d group(P > 0.05). After injecting PTZ we found the SD3d group suffered a serious convulsion.furthermore 2 of which developed to epileptic state and the expression of CB-1 receptor was the lowest among 3 groups(P<0.05).However the TC group did not experience a significant increased or decreased expression of CB1 receptor.DiscussionOur findings indicated that sleep deprivation is a bad stress to the brain which cause neurons apoptosis and functional incapacitation. Suffered from sleep deprivation the expression of cannabinoid receptor 1 mRNA is increased in early stage.With the sleep deprivation prolonging CB1 receptor becomes decomposed and the expression decreased to the lowest level.Continusly, owing to inverse feedback it keeps transient balance for a short time.The data suggested that cannabinoid receptor 1 plays an important protective role in epilepsy. CB1 receptor activation is known to induce hyperpolarization of neuronal membranes,mainly by increasing K+ and decreasing Ca2+ conductance.Such a hyperpolarization,caused by an autocrine or paracrine activation of CB1 receptors by endocannabinoids would decrease the L-glutamate release evoked during excitotoxicity. CB1 receptors mediate protection against excitotoxicity not only by dampening the neuronal excitability of pyramidal neurons but also by inducing intracellular cascades,including ERK phosphorylation and the expression of immediate early genes(IEGs) that code for transcription factors(c-fos and zif 268) and neurotrophins(such as BDNF).Based on our findings we guess the modulation of the expression of CB1 receptor or its agonists may have an anticonvulsant efficiency which may illuminate novel therapeutic targets for the treatment of epilepsy.Conclusions1. Sleep deprivation can cause brain dysfunction and modify the expression of CB1 receptor mRNA.2. The down-regulation of th...