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Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice

Sleep is a recuperative process, and its dysregulation has cognitive, metabolic, and immunological effects that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnor...

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Autores principales: Wheeler, Nicholas D., Ensminger, David C., Rowe, Megan M., Wriedt, Zachary S., Ashley, Noah T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236227/
https://www.ncbi.nlm.nih.gov/pubmed/34221721
http://dx.doi.org/10.7717/peerj.11616
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author Wheeler, Nicholas D.
Ensminger, David C.
Rowe, Megan M.
Wriedt, Zachary S.
Ashley, Noah T.
author_facet Wheeler, Nicholas D.
Ensminger, David C.
Rowe, Megan M.
Wriedt, Zachary S.
Ashley, Noah T.
author_sort Wheeler, Nicholas D.
collection PubMed
description Sleep is a recuperative process, and its dysregulation has cognitive, metabolic, and immunological effects that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammation are not fully understood. To assess the effects of the SNS upon inflammatory responses to SF, C57BL/6j female mice were placed in automated SF chambers with horizontally moving bars across the bottom of each cage at specified intervals to disrupt sleep. Mice were first subjected to either control (no bar movement), acute sleep fragmentation (ASF), or chronic sleep fragmentation (CSF) on a 12:12-h light/dark schedule. ASF involved a bar sweep every 120 s for 24 h, whereas CSF involved a bar sweep every 120 s for 12 h (during 12 L; resting period) over a period of 4 weeks. After exposure to these conditions, mice received an intraperitoneal injection of either phentolamine (5 mg/kg BW; an α-adrenergic receptor blocker), propranolol (5 mg/kg BW; a β-adrenergic receptor blocker), or vehicle (saline). Serum corticosterone concentration, brain and peripheral cytokine (IL1β, TNFα, and TGFβ) mRNA expression, and body mass were assessed. ASF and CSF significantly elevated serum corticosterone concentrations as well as cytokine mRNA expression levels compared with controls, and mice subjected to CSF had decreased body mass relative to controls. Mice subjected to CSF and treated with phentolamine or propranolol had a greater propensity for a decrease in cytokine gene expression compared with ASF, but effects were tissue-specific. Taken together, these results suggest that both α- and β-adrenergic receptors contribute to the SNS mediation of inflammatory responses, and adrenergic antagonists may effectively mitigate tissue-specific SF-mediated inflammation.
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spelling pubmed-82362272021-07-02 Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice Wheeler, Nicholas D. Ensminger, David C. Rowe, Megan M. Wriedt, Zachary S. Ashley, Noah T. PeerJ Genomics Sleep is a recuperative process, and its dysregulation has cognitive, metabolic, and immunological effects that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammation are not fully understood. To assess the effects of the SNS upon inflammatory responses to SF, C57BL/6j female mice were placed in automated SF chambers with horizontally moving bars across the bottom of each cage at specified intervals to disrupt sleep. Mice were first subjected to either control (no bar movement), acute sleep fragmentation (ASF), or chronic sleep fragmentation (CSF) on a 12:12-h light/dark schedule. ASF involved a bar sweep every 120 s for 24 h, whereas CSF involved a bar sweep every 120 s for 12 h (during 12 L; resting period) over a period of 4 weeks. After exposure to these conditions, mice received an intraperitoneal injection of either phentolamine (5 mg/kg BW; an α-adrenergic receptor blocker), propranolol (5 mg/kg BW; a β-adrenergic receptor blocker), or vehicle (saline). Serum corticosterone concentration, brain and peripheral cytokine (IL1β, TNFα, and TGFβ) mRNA expression, and body mass were assessed. ASF and CSF significantly elevated serum corticosterone concentrations as well as cytokine mRNA expression levels compared with controls, and mice subjected to CSF had decreased body mass relative to controls. Mice subjected to CSF and treated with phentolamine or propranolol had a greater propensity for a decrease in cytokine gene expression compared with ASF, but effects were tissue-specific. Taken together, these results suggest that both α- and β-adrenergic receptors contribute to the SNS mediation of inflammatory responses, and adrenergic antagonists may effectively mitigate tissue-specific SF-mediated inflammation. PeerJ Inc. 2021-06-24 /pmc/articles/PMC8236227/ /pubmed/34221721 http://dx.doi.org/10.7717/peerj.11616 Text en ©2021 Wheeler et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Genomics
Wheeler, Nicholas D.
Ensminger, David C.
Rowe, Megan M.
Wriedt, Zachary S.
Ashley, Noah T.
Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice
title Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice
title_full Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice
title_fullStr Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice
title_full_unstemmed Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice
title_short Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice
title_sort alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice
topic Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236227/
https://www.ncbi.nlm.nih.gov/pubmed/34221721
http://dx.doi.org/10.7717/peerj.11616
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