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Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation

Sleep deprivation (SD) is known to impair hippocampus‐dependent memory processes, in part by stimulating the phosphodiesterase (PDE) activity. In the present study, we assessed in mice whether SD also affects spatial pattern separation, a cognitive process that specifically requires the dentate gyru...

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Autores principales: Heckman, Pim R. A., Roig Kuhn, Femke, Raven, Frank, Bolsius, Youri G., Prickaerts, Jos, Meerlo, Peter, Havekes, Robbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285343/
https://www.ncbi.nlm.nih.gov/pubmed/32056276
http://dx.doi.org/10.1002/syn.22150
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author Heckman, Pim R. A.
Roig Kuhn, Femke
Raven, Frank
Bolsius, Youri G.
Prickaerts, Jos
Meerlo, Peter
Havekes, Robbert
author_facet Heckman, Pim R. A.
Roig Kuhn, Femke
Raven, Frank
Bolsius, Youri G.
Prickaerts, Jos
Meerlo, Peter
Havekes, Robbert
author_sort Heckman, Pim R. A.
collection PubMed
description Sleep deprivation (SD) is known to impair hippocampus‐dependent memory processes, in part by stimulating the phosphodiesterase (PDE) activity. In the present study, we assessed in mice whether SD also affects spatial pattern separation, a cognitive process that specifically requires the dentate gyrus (DG) subregion of the hippocampus. Adult male mice were trained in an object pattern separation (OPS) task in the middle of the light phase and then tested 24 hr thereafter. In total, we conducted three studies using the OPS task. In the first study, we validated the occurrence of pattern separation and tested the effects of SD. We found that 6 hr of SD during the first half of the light phase directly preceding the test trial impaired the spatial pattern separation performance. As a next step, we assessed in two consecutive studies whether the observed SD‐induced performance deficits could be prevented by the systemic application of two different PDE inhibitors that are approved for human use. Both the PDE4 inhibitor roflumilast and PDE5 inhibitor vardenafil successfully prevented SD‐induced deficits in spatial pattern separation. As a result, these PDE inhibitors have clinical potential for the prevention of memory deficits associated with loss of sleep.
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spelling pubmed-92853432022-07-15 Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation Heckman, Pim R. A. Roig Kuhn, Femke Raven, Frank Bolsius, Youri G. Prickaerts, Jos Meerlo, Peter Havekes, Robbert Synapse Short Communication Sleep deprivation (SD) is known to impair hippocampus‐dependent memory processes, in part by stimulating the phosphodiesterase (PDE) activity. In the present study, we assessed in mice whether SD also affects spatial pattern separation, a cognitive process that specifically requires the dentate gyrus (DG) subregion of the hippocampus. Adult male mice were trained in an object pattern separation (OPS) task in the middle of the light phase and then tested 24 hr thereafter. In total, we conducted three studies using the OPS task. In the first study, we validated the occurrence of pattern separation and tested the effects of SD. We found that 6 hr of SD during the first half of the light phase directly preceding the test trial impaired the spatial pattern separation performance. As a next step, we assessed in two consecutive studies whether the observed SD‐induced performance deficits could be prevented by the systemic application of two different PDE inhibitors that are approved for human use. Both the PDE4 inhibitor roflumilast and PDE5 inhibitor vardenafil successfully prevented SD‐induced deficits in spatial pattern separation. As a result, these PDE inhibitors have clinical potential for the prevention of memory deficits associated with loss of sleep. John Wiley and Sons Inc. 2020-03-03 2020-06 /pmc/articles/PMC9285343/ /pubmed/32056276 http://dx.doi.org/10.1002/syn.22150 Text en © 2020 The Authors. Synapse published by Wiley Periodicals, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Short Communication
Heckman, Pim R. A.
Roig Kuhn, Femke
Raven, Frank
Bolsius, Youri G.
Prickaerts, Jos
Meerlo, Peter
Havekes, Robbert
Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation
title Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation
title_full Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation
title_fullStr Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation
title_full_unstemmed Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation
title_short Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation
title_sort phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285343/
https://www.ncbi.nlm.nih.gov/pubmed/32056276
http://dx.doi.org/10.1002/syn.22150
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