Sleep deprivation impairs cAMP signalling in the hippocampus

Christopher Vecsey, George Baillie, Devan Jaganath, Robbert Havekes, Andrew Daniels, Mathieu Wimmer, Ted Huang, Kim Brown, Xiang-Yao Li, Giannina Descalzi, Susan Kim, Tao Chen, Yu-Ze Shang, Min Zhuo, Miles Houslay, Ted Abel

Research output: Contribution to journalArticle

241 Citations (Scopus)

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, 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 hippo-campal 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.
Original languageEnglish
Pages (from-to)1122-1125
Number of pages4
JournalNature
Volume461
DOIs
Publication statusPublished - 22 Oct 2009

Keywords

  • phosphodiesterase
  • PDE4
  • rolipram
  • sleep deprivation
  • cognitive enhancement
  • hippocampus
  • synaptic plasticity

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