慢性不可预测轻度应激对大鼠脑电信号及睡眠结构的影响

Effects of Chronic Unpredictable Mild Stress on EEG Signals and Sleep Structure in Rats

摘要: 目的：大鼠慢性不可预测轻度应激(Chronic unpredictable mild stress, CUMS)模型是研究抑郁症发病机制常用的动物模型之一，睡眠障碍是抑郁症的常见伴随症状。本研究通过分析CUMS模型大鼠的脑电信号及睡眠结构变化，为CUMS模型应用于抑郁症睡眠障碍研究提供依据。方法：取雄性SD大鼠分为2组，即正常对照组和模型组，应用7种CUMS进行造模，并使用蔗糖偏好实验、强迫游泳实验及旷场实验进行行为学检测，评价CUMS大鼠的抑郁样行为。采用无线遥测脑电技术对大鼠海马CA3区的脑电信号进行采集和分析。结果：与正常对照组相比，CUMS组大鼠的蔗糖偏好率降低，强迫游泳静止不动时间增加，旷场实验穿越格子数，总移动距离和修饰行为减少，无线遥测脑电数据分析显示CUMS组大鼠Beta和Theta占比明显增加，WAKE占比增加，REM和NREM占比值降低。结论：CUMS大鼠与临床抑郁症患者的EEG和睡眠结构变化有较好一致性，可进一步用于抑郁伴随睡眠障碍的机制研究和药物治疗作用的评价。

Abstract: Objective: The rat chronic unpredictable mild stress (CUMS) model is one of the animal models commonly used to study the pathogenesis of depression, and sleep disturbance is a common concomitant symptom of depression. In this study, we analyzed the Electroencephalogram (EEG) signals and sleep structure changes in CUMS rats to provide a basis for the application of the CUMS model to the study of sleep disorders in depression. Methods: Male SD rats were taken and divided into the control group and the model group. 7 types of CUMS were applied for modeling, and behavioral tests were conducted using the sucrose preference test, the forced swimming test and the open-field test to evaluate the depressive-like behavior of CUMS rats. Wireless telemetry EEG technology was used to collect and analyze the EEG signals in the CA3 region of the rat hippocampus. Results: Compared with the control group, rats in the CUMS group showed decreased sucrose preference rate, increased forced swimming immobility time, and decreased number of crossings in the open-field test, total distance and rearing behaviors. The analysis of the EEG data showed a significant increase in the Beta and Theta occupancy, an increase in the WAKE occupancy, and a decrease in the REM and NREM occupancy values of the rats in the CUMS group. Conclusion: The EEG and sleep structure changes of CUMS rats and clinically depressed patients are in good agreement, which can be further used for the mechanism study of depression accompanied by sleep disorders and the evaluation of drug therapeutic effects.