莫达非尼对REM睡眠剥夺后大鼠认知功能及突触可塑性的影响  

Effect of modafinil on cognition and synaptic plasticity after REM sleep deprivation in rats

作　　者：张琳[1] 郭筱华[1] 赵忠新[1] 黄流清[1] 江波[1] 

机构地区：[1]第二军医大学附属长征医院神经内科,上海200003

出　　处：《中国新药杂志》2007年第20期1674-1678,共5页Chinese Journal of New Drugs

基　　金：上海市科技发展基金(024119029);第二军医大学附属长征医院"十一五""三重三优"学科人才建设计划基金

摘　　要：目的:探讨新型中枢性兴奋剂莫达非尼对不同程度快速动眼(REM)睡眠剥夺与睡眠恢复后大鼠认知功能和大鼠海马突触可塑性的影响。方法:成年雄性SD大鼠随机分为莫达非尼组与对照组,每组分5个不同的REM睡眠剥夺和恢复时间点(SD1d,SD3d,SD5d,SD5d/RS6h,SD5d/RS12h),采用改良多平台水环境REM睡眠剥夺法进行REM睡眠剥夺,利用Y迷宫测定大鼠学习记忆能力,运用蛋白质免疫印记(Western Blot)技术对大鼠海马突触素(SynapsinⅠ)蛋白作选择性半定量分析,免疫组织化学和电镜观察的方法分析大鼠海马CA3区SynapsinⅠ的表达,观察突触可塑性变化。结果:莫达非尼组的错误反应次数(EN)在REM睡眠剥夺后小于对照组,差异有统计学意义(P<0.05),睡眠恢复后两组EN比较,差异无统计学意义(P>0.05),总反应时间(TRT)两组比较,差异也无统计学意义(P>0.05)。Western Blot结果显示SD1d,SD3d,SD5d/RS6h和SD5d/RS12h时莫达非尼组Syn- apsinⅠ表达比对照组增多(P<0.05),SD5d时两组SynapsinⅠ表达无显著差异(P>0.05),免疫组化结果与其一致;电镜下观察SD1d时莫达非尼组的突触联系、突触前膜囊泡数量均较对照组增加。结论:REM睡眠剥夺会引起大鼠认知功能下降,大鼠海马CA3区SynapsinⅠ表达降低,而莫达非尼可以抑制睡眠剥夺后SynapsinⅠ的表达减少,诱导大鼠海马突触可塑性变化,可改善REM睡眠剥夺后的认知行为。Objective： To investigate the effects of modafinil on cognition and synaptic plasiticity in rats after various degrees of sleep deprivation and sleep revival. Methods： Male SD rats were randomly divided into modafinil and control groups. The sleep deprivation model was established by modified multiple platform method. Cognitive function was tested by Y-type maze at 1 d, 3 d, 5 d after sleep deprivation （SD1d, SD3d, SD5d） and at 6 h, 12 h after sleep revival following 5 d sleep deprivation （SD5d/RS6h, SD5d/RS12h）. Rats were sacrificed at each period （SD1d, SD3d, SD5d, SD5d/RS6h, SD5d/RS12h）. The level of synapsin Ⅰ in the hippocampus was quantitatively analyzed by Western Blot technique, and the synapsin Ⅰ expression and synaptic plasticity in the CA3 of hippocampus were determined by immunohistochemistry and electron microscope techniques. Results： There were significant differences （P 〈 0.05） in error reaction numbers, but no significant differences （ P 〉 0. 05 ） in total reaction time, between modafinil and control groups after sleep deprivation. Modafinil significantly increased synapsin Ⅰ expression at 1 d, 3 d after sleep deprivation and at 6 h, 12 h after sleep revival （P 〈 0.05） as detected by Western Blot and immunohistochemistry. The number of synaptic vesicles was raised at SD1d as detected by electron microscopy. Conclusion： Sleep deprivation, no matter mild or severe, exerts adverse effects on cognitive function and synapsin Ⅰ expression. Modafinil improves the cognitive disorder after sleep deprivation and regulates synaptic plasiticity.

关 键 词：快速动相(REM)睡眠剥夺 睡眠恢复 莫达非尼 认知功能 突触可塑性 

分 类 号：R965.1[医药卫生—药理学] R971.7[医药卫生—药学]