Yin Mengmei, Chen Yali, Zheng Hui, Pu Tinglin, Marshall Charles, Wu Ting, Xiao Ming
Department of Neurology, The First Affiliated Hospital of Nanjing Medical University Nanjing, Jiangsu 210029, China.
Jiangsu Province, Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China.
Behav Brain Res. 2017 Mar 15;321:69-78. doi: 10.1016/j.bbr.2016.12.034. Epub 2016 Dec 30.
It has been reported that more than one fourth of the world's population suffers from sleep problems. However, there is not a stable and reliable animal model to mimic the persistent and periodic features of sleep disorders, and correspondingly, the feasibility and effectiveness of repeated behavioral tests remains to be determined. In the present study, we repetitively, and intermittently, treated mice with 3days and 7days of paradoxical sleep deprivation (SD), using the modified multiple small-platforms-over-water method for 3 months. The behavioral results suggested that repeated open field and Y-maze tests are able to successfully detect anxiety-like behaviors and working memory dysfunction of the model mice. The Morris water maze test is not suitable for evaluating spatial learning ability following SD because the long-term utilization of the flower-pot method increases the familiarity of mice with the water environment. Moreover, neuroinflammation, microglial activation and neuronal apoptosis were observed in the hippocampus of model mice even recovery for 3 weeks later. This animal model and corresponding behavioral evaluation method will help to explore the pathogenesis and therapeutic strategies of chronic sleep disorders.
据报道,世界上超过四分之一的人口患有睡眠问题。然而,目前尚无稳定可靠的动物模型来模拟睡眠障碍的持续性和周期性特征,相应地,重复行为测试的可行性和有效性仍有待确定。在本研究中,我们采用改良的多小平台水上法,对小鼠进行了为期3个月的反复、间歇性的3天和7天异相睡眠剥夺(SD)处理。行为学结果表明,重复的旷场试验和Y迷宫试验能够成功检测模型小鼠的焦虑样行为和工作记忆功能障碍。莫里斯水迷宫试验不适用于评估SD后的空间学习能力,因为长期使用花盆法会增加小鼠对水环境的熟悉度。此外,即使在3周后恢复,模型小鼠海马中仍观察到神经炎症、小胶质细胞活化和神经元凋亡。这种动物模型及相应的行为学评估方法将有助于探索慢性睡眠障碍的发病机制和治疗策略。