Department of Neurology, Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China
Brain Res. 2011 Dec 2;1426:38-42. doi: 10.1016/j.brainres.2011.09.002. Epub 2011 Sep 9.
Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats.
先前的研究表明，睡眠剥夺（SD）会损害海马体依赖的认知功能和突触可塑性，而一种新型的促醒剂莫达非尼可预防大鼠 SD 引起的记忆损伤。然而，莫达非尼预防 REM-SD 引起的脑功能损伤的机制仍知之甚少。在本研究中，使用改良的多平台方法对大鼠进行睡眠剥夺，并检测大脑功能。结果表明，莫达非尼治疗可预防 REM-SD 引起的认知功能障碍。与安慰剂相比，莫达非尼治疗组的错误数明显减少，并且背侧海马 CA3 区的突触素 I 表达上调。在莫达非尼处理的大鼠中，与突触可塑性相关的基因 MMP-9 的表达也上调。重要的是，通过特殊的 siRNA 下调 MMP-9 的表达会降低突触素 I 蛋白水平和突触数量。因此，我们证明，莫达非尼通过增加 REM-SD 大鼠中 MMP-9 的表达，至少部分地提高了认知功能和突触可塑性。
