Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus
Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus
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DOI：
10.1016/j.brainres.2004.05.032
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发表时间：
2004-08-20
期刊：
影响因子：
2.9
通讯作者：
Fang, JD
中科院分区：
文献类型：
--
作者：
Guan, ZW;Peng, XW;Fang, JD
睡眠不足可能导致记忆力减退。然而，人们对睡眠不足引起的记忆缺陷的生化基础知之甚少。细胞外信号调节激酶（ERK）参与不同任务的记忆巩固。ERK的磷酸化是其激活所必需的，并且是介导神经元对突触活动反应的重要步骤。本研究的目的是确定完全睡眠剥夺（TSD）对大脑记忆和ERK磷酸化的影响。在Morris水迷宫中训练大鼠在6小时的TSD或自发性睡眠后寻找隐藏平台（空间任务）或可见平台（非空间任务）。创伤后应激障碍对空间学习无影响，但在训练24 h后空间记忆明显受损。非空间学习和记忆没有受到创伤后应激障碍的损害。与对照组相比，6小时睡眠后海马内磷酸化erk水平显著降低，并在2小时恢复性睡眠后恢复到对照组水平。总ERK1和ERK2在6小时睡眠后略有增加，在2小时恢复睡眠后恢复到对照水平。这些改变在创伤后皮层中未被观察到。蛋白磷酸酶-1和丝裂原活化蛋白激酶磷酸酶-2（磷酸化erk）也被测量，但它们没有被TSD改变。空间记忆和ERK磷酸化的损伤表明海马体容易受到睡眠缺失的影响。这些结果与海马体中ERK激活减少与睡眠剥夺引起的空间记忆障碍有关的观点一致。(C) 2004 Elsevier B.V.版权所有
Loss of sleep may result in memory impairment. However, little is known about the biochemical basis for memory deficits induced by sleep deprivation. Extracellular signal-regulated kinase (ERK) is involved in memory consolidation in different tasks. Phosphorylation of ERK is necessary for its activation and is an important step in mediating neuronal responses to synaptic activities. The aim of the present study was to determine the effects of total sleep deprivation (TSD) on memory and ERK phosphorylation in the brain. Rats were trained in Morris water maze to find a hidden platform (a spatial task) or a visible platform (a nonspatial task) after 6 h TSD or spontaneous sleep. TSD had no effect on spatial learning, but significantly impaired spatial memory tested 24 h after training. Nonspatial learning and memory were not impaired by TSD. Phospho-ERK levels in the hippocampus were significantly reduced after 6 h TSD compared to the controls and returned to the control levels after 2 h recovery sleep. Total ERK1 and ERK2 were slightly increased after 6 h TSD and returned to the control levels after 2 h recovery sleep. These alterations were not observed in the cortex after TSD. Protein phosphotase-1 and mitogen-activated protein kinase phosphatase-2, which dephosphorylates phospho-ERK, were also measured, but they were not altered by TSD. The impairments of both spatial memory and ERK phosphorylation indicate that the hippocampus is vulnerable to sleep loss. These results are consistent with the idea that decreased ERK activation in the hippocampus is involved in sleep deprivation-induced spatial memory impairment. (C) 2004 Elsevier B.V. All rights reserved.