Zhang Wen-Hao, Yan Yi-Ning, Williams John P, Guo Jian, Ma Bao-Feng, An Jian-Xiong
Department of Anesthesiology, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beiyuan Rd 3#, Beijing, 100012 China.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049 China.
Sleep Biol Rhythms. 2023 Mar 15;21(3):347-357. doi: 10.1007/s41105-023-00450-8. eCollection 2023 Jul.
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.
The online version contains supplementary material available at 10.1007/s41105-023-00450-8.
本研究旨在探讨右美托咪定对慢性快速眼动(REM)睡眠剥夺大鼠学习记忆障碍的影响及作用机制。将50只雄性Sprague Dawley大鼠随机分为五组。采用改良多平台法造成大鼠睡眠剥夺。通过腹腔注射给予右美托咪定和咪达唑仑。通过莫里斯水迷宫评估学习记忆能力。用透射电子显微镜和高尔基染色检测大鼠海马神经元和突触的形态学变化。通过RNA测序检测各组海马中的基因表达,并通过逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法进行验证。REM睡眠剥夺大鼠表现出空间学习和记忆缺陷。此外,与对照组相比,睡眠剥夺组海马CA1区突触棘密度降低。另外,透射电子显微镜显示,REM睡眠剥夺组海马神经元的突触间隙松散且模糊。有趣的是,右美托咪定治疗使REM睡眠剥夺后的这些指标恢复到对照水平。分子生物学方法显示,与对照组相比,REM睡眠剥夺后Alox15表达显著增加,而右美托咪定给药可逆转Alox15的表达。右美托咪定减轻了慢性REM睡眠剥夺诱导的大鼠空间学习和记忆功能障碍。这种保护作用可能与下调Alox15表达从而增强大鼠海马CA1区突触结构可塑性有关。
网络版包含可在10.1007/s41105-023-00450-8获取的补充材料。