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[交流] Nature：失眠后记忆力减退原因

Nature：失眠后记忆力减退原因

很多人都有过这样的体会，在一晚失眠之后第二天会记性差。美国和英国研究人员最新进行的一项动物实验揭示了其中的生理机制，并发现可以用药物来抵消失眠对记忆造成的不良影响。

美国宾夕法尼亚大学研究人员与英国同行在22日出版的英国《自然》杂志上发表论文介绍说，他们在实验中剥夺了实验鼠5个小时睡眠。结果发现，实验鼠大脑中一种名为PDE4的酶的含量和活性都出现增长，而这种酶会对帮助保持记忆的分子造成影响，从而削弱记忆力。

进一步实验发现，使用可以抑制这种酶的相关药物后，被剥夺睡眠的实验鼠就不会再出现记忆力衰退的现象。这表明在此基础上可以找到有效的药物治疗方案，帮助那些受失眠困扰的人们改善记忆力。

Nature 461, 1122-1125 (22 October 2009) | doi:10.1038/nature08488

Sleep deprivation impairs cAMP signalling in the hippocampus

Christopher G. Vecsey1,2, George S. Baillie3, Devan Jaganath2, Robbert Havekes2, Andrew Daniels2, Mathieu Wimmer1,2, Ted Huang1,2, Kim M. Brown3, Xiang-Yao Li4, Giannina Descalzi4, Susan S. Kim4, Tao Chen4, Yu-Ze Shang4, Min Zhuo4, Miles D. Houslay3 & Ted Abel2

1 Neuroscience Graduate Group,
2 Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
3 Neuroscience and Molecular Pharmacology, Wolfson and Davidson Buildings, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
4 Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
Correspondence to: Ted Abel2 Correspondence and requests for materials should be addressed to T.A.

Millions of people regularly obtain insufficient sleep1. Given the effect 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 models that are dependent on the hippocampus2, 3, 4, 5. Here we have identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. Sleep deprivation selectively impaired 3', 5'-cyclic AMP (cAMP)- and protein kinase A (PKA)-dependent forms of synaptic plasticity6 in the mouse hippocampus, reduced cAMP signalling, and increased activity and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of mice with phosphodiesterase inhibitors rescued the sleep-deprivation-induced deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent memory. These findings demonstrate that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signalling through increased PDE4 activity. Thus, drugs that enhance cAMP signalling may provide a new therapeutic approach to counteract the cognitive effects of sleep deprivation.

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