Cargando…
Sleep deprivation impairs cAMP signaling in the hippocampus
Millions of people regularly obtain insufficient sleep1. 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...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783639/ https://www.ncbi.nlm.nih.gov/pubmed/19847264 http://dx.doi.org/10.1038/nature08488 |
_version_ | 1782174698053828608 |
---|---|
author | Vecsey, Christopher G. Baillie, George S. Jaganath, Devan Havekes, Robbert Daniels, Andrew Wimmer, Mathieu Huang, Ted Brown, Kim M. Li, Xiang-Yao Descalzi, Giannina Kim, Susan S. Chen, Tao Shang, Yu-Ze Zhuo, Min Houslay, Miles D. Abel, Ted |
author_facet | Vecsey, Christopher G. Baillie, George S. Jaganath, Devan Havekes, Robbert Daniels, Andrew Wimmer, Mathieu Huang, Ted Brown, Kim M. Li, Xiang-Yao Descalzi, Giannina Kim, Susan S. Chen, Tao Shang, Yu-Ze Zhuo, Min Houslay, Miles D. Abel, Ted |
author_sort | Vecsey, Christopher G. |
collection | PubMed |
description | Millions of people regularly obtain insufficient sleep1. 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 hippocampus2–5. 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 plasticity6 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. |
format | Text |
id | pubmed-2783639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
spelling | pubmed-27836392010-04-22 Sleep deprivation impairs cAMP signaling in the hippocampus Vecsey, Christopher G. Baillie, George S. Jaganath, Devan Havekes, Robbert Daniels, Andrew Wimmer, Mathieu Huang, Ted Brown, Kim M. Li, Xiang-Yao Descalzi, Giannina Kim, Susan S. Chen, Tao Shang, Yu-Ze Zhuo, Min Houslay, Miles D. Abel, Ted Nature Article Millions of people regularly obtain insufficient sleep1. 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 hippocampus2–5. 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 plasticity6 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. 2009-10-22 /pmc/articles/PMC2783639/ /pubmed/19847264 http://dx.doi.org/10.1038/nature08488 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Vecsey, Christopher G. Baillie, George S. Jaganath, Devan Havekes, Robbert Daniels, Andrew Wimmer, Mathieu Huang, Ted Brown, Kim M. Li, Xiang-Yao Descalzi, Giannina Kim, Susan S. Chen, Tao Shang, Yu-Ze Zhuo, Min Houslay, Miles D. Abel, Ted Sleep deprivation impairs cAMP signaling in the hippocampus |
title | Sleep deprivation impairs cAMP signaling in the hippocampus |
title_full | Sleep deprivation impairs cAMP signaling in the hippocampus |
title_fullStr | Sleep deprivation impairs cAMP signaling in the hippocampus |
title_full_unstemmed | Sleep deprivation impairs cAMP signaling in the hippocampus |
title_short | Sleep deprivation impairs cAMP signaling in the hippocampus |
title_sort | sleep deprivation impairs camp signaling in the hippocampus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783639/ https://www.ncbi.nlm.nih.gov/pubmed/19847264 http://dx.doi.org/10.1038/nature08488 |
work_keys_str_mv | AT vecseychristopherg sleepdeprivationimpairscampsignalinginthehippocampus AT bailliegeorges sleepdeprivationimpairscampsignalinginthehippocampus AT jaganathdevan sleepdeprivationimpairscampsignalinginthehippocampus AT havekesrobbert sleepdeprivationimpairscampsignalinginthehippocampus AT danielsandrew sleepdeprivationimpairscampsignalinginthehippocampus AT wimmermathieu sleepdeprivationimpairscampsignalinginthehippocampus AT huangted sleepdeprivationimpairscampsignalinginthehippocampus AT brownkimm sleepdeprivationimpairscampsignalinginthehippocampus AT lixiangyao sleepdeprivationimpairscampsignalinginthehippocampus AT descalzigiannina sleepdeprivationimpairscampsignalinginthehippocampus AT kimsusans sleepdeprivationimpairscampsignalinginthehippocampus AT chentao sleepdeprivationimpairscampsignalinginthehippocampus AT shangyuze sleepdeprivationimpairscampsignalinginthehippocampus AT zhuomin sleepdeprivationimpairscampsignalinginthehippocampus AT houslaymilesd sleepdeprivationimpairscampsignalinginthehippocampus AT abelted sleepdeprivationimpairscampsignalinginthehippocampus |