期刊
NATURE
卷 461, 期 7267, 页码 1122-U221出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature08488
关键词
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资金
- Systems and Integrative Biology Training [GM07517]
- NIH
- Netherlands Organization for Scientific Research NWO-Rubicon [825.07.029]
- National Institutes of Health [AG017628]
- SCOR [HL060287]
- HFSP [RGSP/2005]
- Medical Research Council (UK)
- European Union [LSHB-CT-2006-037189]
- Fondation Leducq [06CVD02, CIHR84256]
- UK Engineering and Physical Sciences Research Council
- Medical Research Council [G0600765] Funding Source: researchfish
- MRC [G0600765] Funding Source: UKRI
Millions of people regularly obtain insufficient sleep(1). 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 hippocampus(2-5). 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 plasticity(6) 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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