Sharma Rishi, Sahota Pradeep, Thakkar Mahesh M
Harry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri-School of Medicine, Columbia, MO, United States.
Harry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri-School of Medicine, Columbia, MO, United States.
Brain Res. 2021 Jan 1;1750:147155. doi: 10.1016/j.brainres.2020.147155. Epub 2020 Oct 15.
Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric illness affecting > 7 million people every year in the US. Recently, we have shown that the mouse model of predator odor trauma (POT) displayed contextual conditioning and core features of PTSD including sleep disturbances (hyperarousal) and retrieval of traumatic memories following exposure to objective reminders (re-experiencing). PTSD is a disorder of memory function. Since memory consolidation requires the expression of BDNF along with an activation of MAPK/pERK signaling pathway in limbic brain structures (hippocampus and amygdala) and sleep favors memory consolidation, we hypothesized that short-term sleep deprivation (SD, 3 h), immediately after contextual conditioning will attenuate molecular correlates of memory consolidation, sleep disturbances, and memory consolidation. We performed two experiments in adult male C57BL/6J mice to test our hypothesis. Experiment 1 determined the effects of SD on contextual conditioning and changes in sleep wakefulness. Experiment 2 determined the effects of SD on contextual conditioning-induced changes in the expression of BDNF and pERK in hippocampus and amygdala. SD immediately after contextual conditioning (POT + SD group) significantly attenuated sleep disturbances, memory retrieval, and expression of pERK and BDNF in the hippocampus and amygdala as compared to POT-SD group (no SD after contextual conditioning). No significant differences were observed between POT + SD, NOC-SD (no contextual conditioning + no SD), and NOC + SD (no contextual conditioning + SD) groups. Memory consolidation requires sleep and the expression of pERK and BDNF in hippocampus and amygdala immediately after contextual conditioning in POT model of PTSD in mice.
创伤后应激障碍（PTSD）是一种使人衰弱的神经精神疾病，在美国每年影响超过700万人。最近，我们发现捕食者气味创伤（POT）的小鼠模型表现出PTSD的情境条件反射和核心特征，包括睡眠障碍（过度觉醒）以及在接触客观提示物后创伤记忆的恢复（重新体验）。PTSD是一种记忆功能障碍。由于记忆巩固需要脑源性神经营养因子（BDNF）的表达以及边缘脑区结构（海马体和杏仁核）中丝裂原活化蛋白激酶/磷酸化细胞外信号调节激酶（MAPK/pERK）信号通路的激活，并且睡眠有利于记忆巩固，我们推测在情境条件反射后立即进行短期睡眠剥夺（SD，3小时）将减弱记忆巩固、睡眠障碍和记忆巩固的分子相关性。我们在成年雄性C57BL/6J小鼠中进行了两项实验来检验我们的假设。实验1确定了SD对情境条件反射和睡眠-觉醒变化的影响。实验2确定了SD对情境条件反射诱导的海马体和杏仁核中BDNF和pERK表达变化的影响。与POT-SD组（情境条件反射后不进行SD）相比，情境条件反射后立即进行SD（POT+SD组）显著减弱了睡眠障碍、记忆恢复以及海马体和杏仁核中pERK和BDNF的表达。在POT+SD组、NOC-SD组（无情境条件反射+无SD）和NOC+SD组（无情境条件反射+SD）之间未观察到显著差异。在小鼠PTSD的POT模型中，情境条件反射后，记忆巩固需要睡眠以及海马体和杏仁核中pERK和BDNF的表达。
