Post-Exposure Sleep Deprivation Facilitates Correctly Timed Interactions Between Glucocorticoid and Adrenergic Systems, which Attenuate Traumatic Stress Responses
Post-Exposure Sleep Deprivation Facilitates Correctly Timed Interactions Between Glucocorticoid and Adrenergic Systems, which Attenuate Traumatic Stress Responses
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DOI：
10.1038/npp.2012.94
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发表时间：
2012-10-01
影响因子：
7.6
通讯作者：
Cohen, Hagit
中科院分区：
文献类型：
--
作者：
Cohen, Shlomi;Kozlovsky, Nitsan;Cohen, Hagit
可靠的证据支持睡眠在学习和记忆过程中的作用。在啮齿类动物中，睡眠剥夺（SD）会对海马依赖性记忆的巩固产生负面影响。由于记忆是创伤后应激症状不可或缺的一部分，因此在受控、前瞻性的创伤后应激障碍 (PTSD) 动物模型中评估了暴露后 SD 对应激反应各个方面的影响。在暴露于捕食者气味应激后的第一个休息阶段，大鼠被剥夺睡眠 6 小时。 7 天后评估高架十字迷宫和声惊吓反应测试中的行为，并用于将其分类为行为反应组。在第 8 天评估对创伤提醒的冻结反应。每天收集尿液样本以检测皮质酮水平，并测量心率 (HR)。最后，评估了 SD 之前操纵下丘脑-垂体-肾上腺轴和肾上腺素能活性的影响。应激后 10 分钟，系统性施用米非司酮 (MIFE) 和肾上腺素 (EPI)，并在第 7-8 天测量行为反应和对创伤提醒的反应。随后评估了海马糖皮质激素受体（GR）的表达以及树枝化和树突棘的形态学评估。与未治疗的暴露对照组相比，暴露后 SD 有效改善了长期的、压力引起的、类似 PTSD 的行为障碍，减少了创伤提醒冻结反应，并减少了海马 GR 的表达。尽管SD后1小时尿皮质酮水平显着升高且HR减弱，但用MIFE拮抗GR或用EPI刺激肾上腺素能活性有效消除了SD的作用。与暴露的 SD 动物相比，MIFE 和 EPI 处理的动物明显表现出显着较低的总树突长度、较少的分支和沿齿状回树突的较低的脊柱密度，并且在暴露后 8 天GR 表达水平增加。在压力暴露后的早期有意识地阻止睡眠可能有利于减轻创伤性压力相关的后遗症。暴露后 SD 可能会促进糖皮质激素和肾上腺素能系统之间正确定时的相互作用，从而破坏厌恶或恐惧记忆的巩固。神经精神药理学 (2012) 37, 2388-2404; doi：10.1038/npp.2012.94； 2012 年 6 月 20 日在线发布
Reliable evidence supports the role of sleep in learning and memory processes. In rodents, sleep deprivation (SD) negatively affects consolidation of hippocampus-dependent memories. As memory is integral to post-traumatic stress symptoms, the effects of post-exposure SD on various aspect of the response to stress in a controlled, prospective animal model of post-traumatic stress disorder (PTSD) were evaluated. Rats were deprived of sleep for 6 h throughout the first resting phase after predator scent stress exposure. Behaviors in the elevated plus-maze and acoustic startle response tests were assessed 7 days later, and served for classification into behavioral response groups. Freezing response to a trauma reminder was assessed on day 8. Urine samples were collected daily for corticosterone levels, and heart rate (HR) was also measured. Finally, the impact of manipulating the hypothalamus-pituitary-adrenal axis and adrenergic activity before SD was assessed. Mifepristone (MIFE) and epinephrine (EPI) were administered systemically 10-min post-stress exposure and behavioral responses and response to trauma reminder were measured on days 7-8. Hippocampal expression of glucocorticoid receptors (GRs) and morphological assessment of arborization and dendritic spines were subsequently evaluated. Post-exposure SD effectively ameliorated long-term, stress-induced, PTSD-like behavioral disruptions, reduced trauma reminder freezing responses, and decreased hippocampal expression of GR compared with exposed-untreated controls. Although urine corticosterone levels were significantly elevated 1 h after SD and the HR was attenuated, antagonizing GRs with MIFE or stimulation of adrenergic activity with EPI effectively abolished the effect of SD. MIFE- and EPI-treated animals clearly demonstrated significantly lower total dendritic length, fewer branches and lower spine density along dentate gyrus dendrites with increased levels of GR expression 8 days after exposure, as compared with exposed-SD animals. Intentional prevention of sleep in the early aftermath of stress exposure may well be beneficial in attenuating traumatic stress-related sequelae. Post-exposure SD may disrupt the consolidation of aversive or fearful memories by facilitating correctly timed interactions between glucocorticoid and adrenergic systems. Neuropsychopharmacology (2012) 37, 2388-2404; doi:10.1038/npp.2012.94; published online 20 June 2012