Sleep deprivation impairs cAMP signalling in the hippocampus Export

@article{Vecsey:Nature:2009, 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.}, author = {Vecsey, Christopher G. and Baillie, George S. and Jaganath, Devan and Havekes, Robbert and Daniels, Andrew and Wimmer, Mathieu and Huang, Ted and Brown, Kim M. and Li, Xiang-Yao and Descalzi, Giannina and Kim, Susan S. and Chen, Tao and Shang, Yu-Ze and Zhuo, Min and Houslay, Miles D. and Abel, Ted}, citeulike-article-id = {5983189}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature08488}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature08488}, day = {22}, doi = {10.1038/nature08488}, issn = {0028-0836}, journal = {Nature}, keywords = {hippocampus, sleep\_derivation}, month = {October}, number = {7267}, pages = {1122--1125}, posted-at = {2009-11-04 10:45:01}, priority = {2}, publisher = {Nature Publishing Group}, title = {Sleep deprivation impairs cAMP signalling in the hippocampus}, url = {http://dx.doi.org/10.1038/nature08488}, volume = {461}, year = {2009} }

TY - JOUR ID - Vecsey:Nature:2009 L3 - citeulike-article-id:5983189 N2 - 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. IS - 7267 JF - Nature SN - 0028-0836 EP - 1125 TI - Sleep deprivation impairs cAMP signalling in the hippocampus PB - Nature Publishing Group VL - 461 SP - 1122 KW - hippocampus KW - sleep_derivation AU - Vecsey, Christopher AU - Baillie, George AU - Jaganath, Devan AU - Havekes, Robbert AU - Daniels, Andrew AU - Wimmer, Mathieu AU - Huang, Ted AU - Brown, Kim AU - Li, Xiang-Yao AU - Descalzi, Giannina AU - Kim, Susan AU - Chen, Tao AU - Shang, Yu-Ze AU - Zhuo, Min AU - Houslay, Miles AU - Abel, Ted PY - 2009/10/22/ UR - http://dx.doi.org/10.1038/nature08488 ER -