Journal article
Sleep deprivation impairs cAMP signaling in the hippocampus
Nature (London), Vol.461(7267), pp.1122-1125
10/22/2009
DOI: 10.1038/nature08488
PMCID: PMC2783639
PMID: 19847264
Abstract
Millions of people regularly obtain insufficient sleep
1
. 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
2
–
5
. 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
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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.
Details
- Title: Subtitle
- Sleep deprivation impairs cAMP signaling in the hippocampus
- Creators
- Christopher G Vecsey - Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA, 19104George S Baillie - Neuroscience and Molecular Pharmacology, Wolfson and Davidson Buildings, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UKDevan Jaganath - Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104Robbert Havekes - Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104Andrew Daniels - Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104Mathieu Wimmer - Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA, 19104Ted Huang - Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA, 19104Kim M Brown - Neuroscience and Molecular Pharmacology, Wolfson and Davidson Buildings, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UKXiang-Yao Li - Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, CanadaGiannina Descalzi - Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, CanadaSusan S Kim - Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, CanadaTao Chen - Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, CanadaYu-Ze Shang - Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, CanadaMin Zhuo - Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, CanadaMiles D Houslay - Neuroscience and Molecular Pharmacology, Wolfson and Davidson Buildings, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UKTed Abel - Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.461(7267), pp.1122-1125
- DOI
- 10.1038/nature08488
- PMID
- 19847264
- PMCID
- PMC2783639
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 10/22/2009
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065824002771
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