Dexmedetomidine prevents spatial learning and memory impairment induced by chronic REM sleep deprivation in rats

The study was attempted to investigate the effect on and mechanisms of action of dexmedetomidine with regard to learning and memory impairment in rats with chronic rapid eye movement (REM) sleep deprivation. A total of 50 male Sprague Dawley rats were randomly divided into five groups. Modified multiple platform method was conducted to cause the sleep deprivation of rats. Dexmedetomidine and midazolam were administered by intraperitoneal injection. Learning and memory ability was assessed through Morris water maze. Morphological changes of rat hippocampal neurons and synaptic were detected by transmission electron microscope and Golgi staining. The gene expression in hippocampus of each group was detected by RNA-seq and verified by RT-PCR and western blot. REM Sleep-deprived rats exhibited spatial learning and memory deficits. Furthermore, there was decreased density of synaptic spinous in the hippocampal CA1 region of the sleep deprivation group compared with the control. Additionally, transmission electron microscopy showed that the synaptic gaps of hippocampal neurons in REM sleep deprivation group were loose and fuzzy. Interestingly, dexmedetomidine treatment normalized these events to control levels following REM sleep deprivation. Molecular biological methods showed that Alox15 expression increased significantly after REM sleep deprivation as compared to control, while dexmedetomidine administration reversed the expression of Alox15. Dexmedetomidine alleviated the spatial learning and memory dysfunction induced with chronic REM sleep deprivation in rats. This protective effect may be related to the down-regulation of Alox15 expression and thereby the enhancement of synaptic structural plasticity in the hippocampal CA1 area of rats.