The Effect of REM Sleep Deprivation on the Expression of ATF-6α and CHOP in the Rat Cerebral Corte and Drug Intervention

To explore the possible ATF-6 activate signal pathway and pro-apoptosis factor CHOP/GADD153 role during sleep deprivation(SD) and the neuroprotective effect of Meclofenoxate Hydrochloride through observing the expression changes of ATF-6αand CHOP/GADD153 in the rat cerebral cortex during different stages of rapid eye movement(REM) sleep deprivation;The rat REM sleep deprivation model was established by the modified multiple platform method(MMPM).All the male SD rats were divided randomly into five groups:cage control group(CC,n=10),tank control group(TC,n=10),sleep deprivation model group(n=30),saline group(n=30) and Meclofenoxate Hydrochloride group(n=30).The expression and distribution ATF-6αand CHOP in the rat cerebral cortex were observed by immunofluorescence. The semi-quantitative level of ATF-6αand CHOP protein in the rat cerebral cortex were analyzed by Western-blot.Immunofluorescence analysis of ATF-6αshowed in cytoplasm and nuclear in rat cortex,and ATF-6αprotein levels increased after 1 day's sleep deprivation,reached the highest expression on 3 sleep deprivation,and began to decrease on 5 days'sleep deprivation.Immunofluorescence staining of CHOP revealed red signal in nuclear,and the expression of CHOP in cerebral cortex started from 1 day's sleep deprivation and gradually increased after 3 days'sleep deprivation,then reached the highest on 5 days'sleep deprivation.The expression of ATF-6αand CHOP protein reduced sharply in the group administrated by Meclofenoxate Hydrochloride;Short-time REM sleep deprivation may lead to the overexpression of ATF-6αin the rat cerebral cortex,which may induce the UPR pathway of endoplasmic reticulum stress.CHOP was activated after long-time REM sleep deprivation,and may arouse ER-related apoptosis pathway at last.It is possible that the neuroprotective effect of Meclofenoxate Hydrochloride may be induced by reducing the ER stress level and suppressing cell apoptosis.