Effects Of REM Sleep Deprivation On Spatial Learning And Memory And Hippocampal Neurogenesis In Rats

ObjectiveTo observe the effects of72hours Rapid Eye Movement(REM) sleep deprivation(SD)and12hours sleep revival on spatial learning and memory ablity,neurogenesis and synapticplasticity in the hippocampus of rats,and to explore the mechanism of cognitive disordercaused by REM SD.MethodsSixty healthy male SD rats were randomly divided into3groups: cage controlgroup(CC), REM sleep deprivation group(SD) and sleep revival group(RS). The modifiedmultiple platform method(MMPM)was used to establish sleep deprivation model for72hous REM sleep deprivation of rats,the cognitive function was tested by Morris Water Maze.Rats of BrdU injected group received intraperitoneal injection of BrdU100mg/kg weighttwice daily for7consecutive days starting from the beginning of sleep deprivation.The ratswere sacrificed after the Morris Water Maze task was over.Immunohistochemistry was usedto observe the cell proliferation in hippocampus of rats,while immunofluoresent triplelabeling was processed to examine the phenotype of the newly generated cells. NR2B andPSD-95levels in hippocampus of rats were tested with Western blot technique. Apoptosisof hippocampal neuron was detected by TUNEL assay. Sleep revival group were given12hours sleep revival after REM sleep deprivation,then given the same treatments as othergroups.ResultsThe average escape latency in SD and RS groups of MWM navigation test were longerthan that in CC group.In space exploration experiment,the rats of SD and RS groups spentless time in the target quadrant than that in CC group. Compared with SD group,the rats of RS group had shorter average escape latency and more percentage of the time in targetquadrant.There were no significant differences of swimming speed between groups.Through immunohistochemistry method, typical BrdU positive cells were observed indentate gyrus under the optical microscope.Brown granules are in the nuclei,not thecytoplasm and cell membrane.The average numbers of BrdU positive cells in SD and RSgroups were significantly lower than that in CC group (P<0.01),but there were nosignificant differences between SD and RS group.Immunofluoresent triple labeling showedthat there had no differences of phenotype of BrdU positive cells between each groups.Results of Western blot for NR2B and PSD-95revealed that the NR2B and PSD-95levelsin hippocampus in both SD and RS groups were significantly lower than that in CCgroup(P<0.05). Compared with SD group,NR2B and PSD-95expressions in RS group wereincreased by Western Blot. There were no TUNEL positive cells in hippocampus in allgroups.ConclusionREM sleep deprivation could have adverse effects on spatial learning and memoryablity,the proliferation of hippocampal neurons and NR2B、 PSD-95expressions inrats.There was partial improvement on cognitive function after sleep revival.The decreaseof neuronal proliferation and the reduction of synaptic plasticity in the hippocampus may beone of the mechanisms of cognitive decline caused by sleep deprivation.