Sleep deprivation impairs cAMP signalling in the hippocampus.
Sleep deprivation impairs cAMP signalling in the hippocampus.
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数百万人经常睡眠不足。鉴于睡眠剥夺对我们生活的影响，了解睡眠剥夺影响的细胞和分子途径显然具有社会和临床重要性。睡眠不足对大脑的主要影响之一是在依赖海马体的学习范式中产生记忆缺陷。在这项研究中，我们确定了短暂睡眠剥夺改变海马功能的分子机制。睡眠剥夺选择性地损害海马中 cAMP/PKA 依赖性突触可塑性，减少 cAMP 信号传导，并增加磷酸二酯酶 4 (PDE4)（一种降解 cAMP 的酶）的活性和蛋白质水平。 PDE 抑制剂治疗可以挽救睡眠剥夺引起的 cAMP 信号传导、突触可塑性和海马依赖性记忆的缺陷。这些发现表明，短暂的睡眠剥夺会通过增加 PDE4 活性来干扰 cAMP 信号传导，从而破坏海马功能。因此，增强 cAMP 信号传导的药物可能提供一种新的治疗方法来抵消睡眠剥夺对认知的影响。
Millions of people regularly obtain insufficient sleep. Given the impact of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to produce memory deficits in learning paradigms that are dependent on the hippocampus. In this study, we have identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. Sleep deprivation selectively impaired cAMP/PKA-dependent forms of synaptic plasticity in the hippocampus, reduced cAMP signaling, and increased activity and protein levels of phosphodiesterase-4 (PDE4), an enzyme that degrades cAMP. Treatment with PDE inhibitors rescued the sleep deprivation-induced deficits in cAMP signaling, synaptic plasticity, and hippocampus-dependent memory. These findings demonstrate that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signaling through increased PDE4 activity. Thus drugs that enhance cAMP signaling may provide a novel therapeutic approach to counteract the cognitive effects of sleep deprivation.
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