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Cited by 454Sleep and Wakefulness ResearchSleep and Work-Related FatigueMemory and Neural Mechanisms

Sleep deprivation impairs cAMP signalling in the hippocampus

Open access
Vecsey, Christopher G., Baillie, George S., Jaganath, Devan, Havekes, Robbert, Daniels, Andrew, Wimmer, Mathieu, Huang, Ted, Brown, Kim M. +8 more·2009·Nature
DOI 10.1038/nature08488PMC PMC2783639
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Abstract

Millions of people regularly obtain insufficient sleep. 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. 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 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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  • In mice, rolipram immediately and 2.5 h after contextual fear conditioning prevented impairing effect of sleep deprivation on retention of freezing response.

    “In mice, treatment with the selective phosphodiesterases (PDE) 4 inhibitor rolipram immediately and 2.5 h after single-trial contextual fear conditioning prevented the impairing effect of sleep deprivation on retention of the freezing response to the conditioned context (1246).”

    From About Sleep's Role in Memory (2013) · cites this paper as [1246]

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Authors
Vecsey, C. G., Baillie, G. S., Jaganath, D., Havekes, R., Daniels, A., Wimmer, M., Huang, T., Brown, K. M., Li, X.-Y., Descalzi, G., Kim, S. S., Chen, T., Shang, Y.-Z., Zhuo, M., Houslay, M. D., & Abel, T.
Affiliations
  • University of Pennsylvania (US)
  • University of Glasgow (GB)
  • University of Toronto (CA)
Corresponding author
Abel, Ted
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2009-10
Volume
461
Issue
7267
Pages
1122-1125
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature08488
PMC
PMC2783639
OpenAlex
W2067780273
Cited by
454
References
4
Citations by year
2026: 26 · 2025: 28 · 2024: 45 · 2023: 18 · 2022: 29 · 2021: 24 · 2020: 33 · 2019: 22 · 2018: 28 · 2017: 24 · 2016: 13 · 2015: 24 · 2014: 38 · 2013: 25 · 2012: 21
FWCI
12.30
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • TUScholarShare (Temple University) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (825.07.029)
  • Canadian Institutes of Health Research (84256)
  • National Institute on Aging (P01AG017628, AG017628)
  • National Heart, Lung, and Blood Institute (HL07953, P50HL060287, HL060287, T32HL007953)
  • National Institute of General Medical Sciences (T32GM007517, GM-07517)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
sleep deprivation, cAMP signaling, protein kinase A, hippocampus, synaptic plasticity, phosphodiesterase 4, phosphodiesterase inhibitors, memory impairment, learning deficits, cognitive impairment, therapeutic target
MeSH terms
Cyclic AMP, Animals, Colforsin, Hippocampus, Male, Memory, Mice, Inbred C57BL, Neuronal Plasticity, Sleep Deprivation, Time Factors, Second Messenger Systems, Long-Term Potentiation, Cyclic AMP-Dependent Protein Kinases, Rolipram, Mice, Cyclic Nucleotide Phosphodiesterases, Type 4, Phosphodiesterase 4 Inhibitors

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