快速眼动睡眠剥夺对中枢5-羟色胺缺失小鼠orexin阳性神经元活性的影响  

Effect of rapid eye movement sleep deprivation on neural activity of orexin-positive neurons in central serotonin deficient mice

作　　者：邹慧莉[1] 赵广宇[1] 宿长军[1] 李柱一[1] 

机构地区：[1]第四军医大学唐都医院神经内科,西安710038

出　　处：《神经解剖学杂志》2009年第3期312-316,共5页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(30870807)资助项目

摘　　要：为探讨中枢5羟色胺(5-HT)的缺失对正常睡眠和快速眼动睡眠剥夺(REM sleep deprivation)情况下orexin阳性神经元活动的影响,本研究利用中枢5-HT神经元缺失的条件性基因敲除小鼠(Pet1-Cre/Lmx1b flox/flox CKO小鼠),采用小平台水环境法建立小鼠快速眼动睡眠剥夺模型,免疫组化方法观察野生型小鼠和中枢5-HT神经元缺失小鼠在正常睡眠状态及8 h快速眼动睡眠剥夺后下丘脑内orexin阳性神经元的数量,免疫组化双标法观察orexin/c-fos双标神经元占orexin阳性神经元的比例。结果显示:CKO小鼠睡眠剥夺前后orexin阳性神经元的数量未见明显差别,与野生型小鼠相比亦未见统计学差别;在正常睡眠状态下(对照组),CKO小鼠orexin/c-fos双标神经元的数量与野生型小鼠相当,但睡眠剥夺后明显低于野生型小鼠睡眠剥夺组。本研究结果提示,作为维持觉醒的重要神经递质5-HT的缺失可能降低了中枢神经系统的觉醒水平,致使睡眠剥夺不能提高促发和维持觉醒的orexin阳性神经元的活性。To study the effect of central serotonin deficiency on the activity of orexin-expression neurons under normal sleep and rapid eye movement （REM） sleep deprived conditions, the central serotonin deficient nfiee （Petl-Cre/Lmxl b flox/flox CKO mice） and small plat- form method was used to establish mouse model of REM sleep deprivation. Immunohistochemical method was performed to observe total number of orexin-positive neurons of both wild type and central serotonin deficient mice under normal sleep condition or 8 h REM sleep deprivation. Then double immunostaining was used to detect orexin/c-fos double-labeled cells and the percentage to total orexin-positive neurons was calculated. The results showed that total number of orexin-positive neurons was not changed under both normal sleep and REM sleep deprivation and there were not differences between the two genotypes. However, the percentage of orexin/c-fos double-labeled cells was significantly decreased in CKO mice after REM sleep deprivation compared with wild type littermates. The present results indicate that, the deficiency of serotonin, an important neural transmitter in sleep-wake regulation in central nervous system, may decrease the level of waking and fail to enhance the neural activity of orexin-expressing neurons after REM sleep deprivation.

关 键 词：5羟色胺 快速眼动睡眠剥夺 orexln 中枢5-HT缺失小鼠 

分 类 号：R363[医药卫生—病理学]