中华神经科杂志
中華神經科雜誌
중화신경과잡지
Chinese Journal of Neurology
2015年
1期
44-49
,共6页
窦伟%李振%张照环%黄流清%赵忠新
竇偉%李振%張照環%黃流清%趙忠新
두위%리진%장조배%황류청%조충신
睡眠剥夺%认知障碍%记忆%PrPC蛋白质类%轴突
睡眠剝奪%認知障礙%記憶%PrPC蛋白質類%軸突
수면박탈%인지장애%기억%PrPC단백질류%축돌
Sleep deprivation%Cognition disorders%Memory%PrPC proteins%Axons
目的 研究快速眼动睡眠剥夺后大鼠空间记忆功能和海马细胞型朊蛋白(cellular prion protein,PrPC)表达的变化及沉默细胞型朊蛋白对体外培养的海马神经元轴突延伸的影响,探讨睡眠剥夺后认知功能变化的机制.方法 成年SD大鼠按体重大小排序,完全随机法分为3组,分别为正常笼养对照组、水槽对照组、睡眠剥夺组.采用改良多平台睡眠剥夺法进行连续72 h快速眼动睡眠剥夺.采用Moms水迷宫评估空间记忆.用蛋白质印迹法检测睡眠剥夺后各组大鼠海马PrPC表达的变化.使用原代培养的海马神经元,用RNA干扰技术沉默PrPC,观察神经元轴突延伸的变化.结果 大鼠睡眠剥夺后空间记忆受损,睡眠剥夺组穿越平台次数(3.17±0.95)较笼养对照组(7.17±0.95)和水槽对照组(6.50 ±0.62)明显减少(Z =2.026 6,Z=2.026 6,P＜0.05),平台接近平均值(mm)睡眠剥夺组(711.74 ±33.99)较笼养对照组(592.32±31.31)和水槽对照组(580.86±11.36)明显增大(Z=-2.001 6,Z=-2.482 0,P＜0.05).睡眠剥夺后海马PrPC的表达睡眠剥夺组(0.33±0.10)较笼养对照组(1.01±0.33)和水槽对照组(0.96±0.27)明显下调(Z =2.152 9,Z=2.152 9,P＜0.05).沉默PrPC导致原代培养的海马神经元轴突延伸障碍,感染组神经元(326.28±12.53)与未感染组(555.00±30.43)和感染阴性对照组(558.70±23.10)比较,轴突长度(μm)明显变短(Z =4.768 4,Z=4.877 0,P＜0.05).结论 睡眠剥夺后PrPC介导的海马新生神经元轴突延伸障碍可能是睡眠剥夺后认知障碍发生的潜在机制之一.
目的 研究快速眼動睡眠剝奪後大鼠空間記憶功能和海馬細胞型朊蛋白(cellular prion protein,PrPC)錶達的變化及沉默細胞型朊蛋白對體外培養的海馬神經元軸突延伸的影響,探討睡眠剝奪後認知功能變化的機製.方法 成年SD大鼠按體重大小排序,完全隨機法分為3組,分彆為正常籠養對照組、水槽對照組、睡眠剝奪組.採用改良多平檯睡眠剝奪法進行連續72 h快速眼動睡眠剝奪.採用Moms水迷宮評估空間記憶.用蛋白質印跡法檢測睡眠剝奪後各組大鼠海馬PrPC錶達的變化.使用原代培養的海馬神經元,用RNA榦擾技術沉默PrPC,觀察神經元軸突延伸的變化.結果 大鼠睡眠剝奪後空間記憶受損,睡眠剝奪組穿越平檯次數(3.17±0.95)較籠養對照組(7.17±0.95)和水槽對照組(6.50 ±0.62)明顯減少(Z =2.026 6,Z=2.026 6,P＜0.05),平檯接近平均值(mm)睡眠剝奪組(711.74 ±33.99)較籠養對照組(592.32±31.31)和水槽對照組(580.86±11.36)明顯增大(Z=-2.001 6,Z=-2.482 0,P＜0.05).睡眠剝奪後海馬PrPC的錶達睡眠剝奪組(0.33±0.10)較籠養對照組(1.01±0.33)和水槽對照組(0.96±0.27)明顯下調(Z =2.152 9,Z=2.152 9,P＜0.05).沉默PrPC導緻原代培養的海馬神經元軸突延伸障礙,感染組神經元(326.28±12.53)與未感染組(555.00±30.43)和感染陰性對照組(558.70±23.10)比較,軸突長度(μm)明顯變短(Z =4.768 4,Z=4.877 0,P＜0.05).結論 睡眠剝奪後PrPC介導的海馬新生神經元軸突延伸障礙可能是睡眠剝奪後認知障礙髮生的潛在機製之一.
목적 연구쾌속안동수면박탈후대서공간기억공능화해마세포형원단백(cellular prion protein,PrPC)표체적변화급침묵세포형원단백대체외배양적해마신경원축돌연신적영향,탐토수면박탈후인지공능변화적궤제.방법 성년SD대서안체중대소배서,완전수궤법분위3조,분별위정상롱양대조조、수조대조조、수면박탈조.채용개량다평태수면박탈법진행련속72 h쾌속안동수면박탈.채용Moms수미궁평고공간기억.용단백질인적법검측수면박탈후각조대서해마PrPC표체적변화.사용원대배양적해마신경원,용RNA간우기술침묵PrPC,관찰신경원축돌연신적변화.결과 대서수면박탈후공간기억수손,수면박탈조천월평태차수(3.17±0.95)교롱양대조조(7.17±0.95)화수조대조조(6.50 ±0.62)명현감소(Z =2.026 6,Z=2.026 6,P＜0.05),평태접근평균치(mm)수면박탈조(711.74 ±33.99)교롱양대조조(592.32±31.31)화수조대조조(580.86±11.36)명현증대(Z=-2.001 6,Z=-2.482 0,P＜0.05).수면박탈후해마PrPC적표체수면박탈조(0.33±0.10)교롱양대조조(1.01±0.33)화수조대조조(0.96±0.27)명현하조(Z =2.152 9,Z=2.152 9,P＜0.05).침묵PrPC도치원대배양적해마신경원축돌연신장애,감염조신경원(326.28±12.53)여미감염조(555.00±30.43)화감염음성대조조(558.70±23.10)비교,축돌장도(μm)명현변단(Z =4.768 4,Z=4.877 0,P＜0.05).결론 수면박탈후PrPC개도적해마신생신경원축돌연신장애가능시수면박탈후인지장애발생적잠재궤제지일.
Objective To investigate the effect of rapid eye movement (REM) sleep deprivation on spatial memory and hippocampal cellular prion protein (PrPC) expression and to explore the underlying mechanism of cognitive impairment induced by sleep deprivation.Methods Adult Sprague-Dawley rats were sorted by weight,randomly divided into three groups:the cage control (CC) group,the tank control (TC) group,and the sleep deprivation (SD) group.Rats were deprived of REM sleep for 72 h using the modified multiple platform method.The Morris water maze task was used to assess hippocampal-dependent spatial memory.After sleep deprivation,the rats were sacrificed and their brain tissue was analyzed for PrPC protein expression via Western blotting.Hippocampal neuron axon elongation was examined as well after lentivector-mediated RNA interference (RNAi) of PrPC in primary cultured rat hippocampal neurons.Results REM sleep deprivation for 72 h resulted in spatial memory impairment.The number of times of rats passing through the platform was decreased significantly in the SD group (3.17 ±0.95) compared with the CC (7.17 ±0.95) and TC (6.50 ±0.62) groups (Z =2.026 6,Z =2.026 6,P ＜0.05),the mean value of proximity to the platform (mm) was greater for rats of the SD group (711.74 ± 33.99) compared to those of theCC (592.32±31.31) andTC (580.86±11.36) groups (Z=-2.001 6,Z=-2.4820,P ＜ 0.05).REM sleep deprivation for 72 h resulted in reduced PrPC level in the hippocampus (0.33 ± 0.10) compared with the CC (1.01 ±0.33) and TC (0.96 ±0.27) groups (Z=2.152 9,Z=2.152 9,P ＜ 0.05).In primary cultured hippocampal neurons,axon elongation(μm) was inhibited 7 days in infected neurons (326.28 ± 12.53) compared with normal (555.00 ±30.43) or negative control (558.70 ±23.10) cells (Z =4.768 4,Z =4.877 0,P ＜ 0.05).Conclusion These findings suggest that PrPC-mediated hippocampal neuron axon elongation inhibition is probably involved in spatial memory impairment induced by sleep deprivation in rats.
