Vecsey, C. G. et al. (2009) Sleep deprivation impairs cAMP signalling in the hippocampus. Nature, 461(7267), pp. 1122-1125. (doi: 10.1038/nature08488)
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Publisher's URL: http://dx.doi.org/10.1038/nature08488
Abstract
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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Houslay, Professor Miles and Baillie, Professor George |
| 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., and Abel, T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | Nature |
| Publisher: | Nature Publishing Group |
| ISSN: | 0028-0836 |
| ISSN (Online): | 1476-4687 |
| Related URLs: |
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