REM睡眠剥夺对帕金森病大鼠识别记忆损害的影响及与AQP4蛋白表达的相关性

Effect of REM sleep deprivation on cognitive deterioration and its relation to aquaporin-4 expression in a rat model of Parkinson’s disease

目的:观察快速眼动(REM)睡眠剥夺(REMSD)对帕金森病(PD)模型大鼠认知功能的影响,探讨REMSD与PD相关认知损害及水通道蛋白4(AQP4)表达的关系。方法:采用单侧黑质内定向注射6-羟多巴胺(6-OHDA)建立PD大鼠模型,以REMSD干预1周或维持正常睡眠,分为4组(每组大鼠数量n=6)——假手术组、REMSD+假手术组、正常睡眠的PD大鼠组、REMSD干预的PD大鼠组。采用新物体识别(NOR)实验评估各组大鼠的识别记忆。测试结束后,采用蛋白质印迹和免疫荧光分析检测各组大鼠皮层与海马中α-突触核蛋白和AQP4蛋白的表达。结果:REMSD干预后的PD大鼠其识别记忆优于正常睡眠的PD大鼠(P<0.05),REMSD干预后的PD大鼠皮层和海马中α-突触核蛋白的表达明显低于正常睡眠的PD大鼠(P<0.05)。而REMSD干预后的PD大鼠皮层和海马中AQP4蛋白的表达水平则明显高于正常睡眠的PD大鼠(P<0.05)。结论:REMSD减轻PD相关认知损害,与皮层和海马中α-突触核蛋白表达减少、AQP4蛋白表达增加相关。REM睡眠与AQP4蛋白表达的调控对改善PD相关认知损害的作用与机制有待进一步研究。

Objective: To observe the effects of rapid eye movement(REM) sleep deprivation(REMSD) on cognitive function of rats with Parkinson’s disease(PD), and to explore the relationship between REMSD/cognitive impairment associated with PD and aquaporin-4(AQP4) expression. Methods:Unilateral stereotaxic intranigra injection of 6-hydroxydopamine(6-OHDA) in rats was performed to induce the animal models of PD. Rats were then exposed to one week of REMSD or normal sleep,and divided into four groups(n=6, respectively): sham operation group, REMSD+sham operation group, PD+normal sleep group, and PD+REMSD intervention group. Then, novel object recognition(NOR) test was taken to evaluate the recognition memory. Finally, rat brains were collected for the Western Blot and immunofluorescence analysis of α-synuclein and AQP4 in hippocampus and cortex. Results: PD rats with REMSD had significantly less α-synuclein deposition but more AQP4 expression in hippocampus and cortex as compared with PD rats with normal sleep. Consistently, the recognition memory ability of PD rats with REMSD was better than that of PD rats with normal sleep. Conclusion: REMSD prevented cognitive deterioration associated with PD, and associated with decreased deposition of α-synuclein and enhanced expression of AQP4 in hippocampus and cortex. Mechanism of REM sleep regulation and AQP4 protein expression in the cognitive improvement of PD remains to be further studied.