{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:59:09Z","timestamp":1785232749024,"version":"3.55.0"},"reference-count":32,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R15GM117534-02"],"award-info":[{"award-number":["R15GM117534-02"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["P20GM103436-22"],"award-info":[{"award-number":["P20GM103436-22"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009498","name":"Western Kentucky University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009498","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Disrupted sleep from obstructive sleep apnea or insomnia promotes an inflammatory environment. Studies in mice have shown that experimental sleep fragmentation (SF) increases pro-inflammatory cytokine gene expression in the brain and peripheral tissues as well as increases circulating glucocorticoids. Although glucocorticoids classically exert anti-inflammatory effects at pharmacological concentrations, they may also modulate immune function in a context- and dose-dependent manner. To investigate whether glucocorticoids regulate pro-inflammatory responses, we used a classical adrenalectomy (ADX) ablation and corticosterone (CORT) replacement design. Adult male C57BL\/6J mice received bilateral ADX, sham surgery, or ADX with CORT replacement in drinking water and were exposed to acute (24\u2005h) SF or no SF (NSF). Pro-inflammatory gene expression (interleukin-1 beta and tumor necrosis factor-alpha) was quantified in the hippocampus, hypothalamus, and prefrontal cortex, as well as peripheral tissues including the liver, spleen, heart, and epididymal white adipose tissue. ADX effectively reduced serum CORT, while CORT replacement produced pharmacological hormone levels. Pharmacological CORT treatment robustly suppressed pro-inflammatory gene expression across multiple brain regions (prefrontal cortex, hypothalamus) and peripheral tissues (liver, heart, spleen) compared with ADX and\/or sham mice, indicating a strong anti-inflammatory effect at elevated glucocorticoid concentrations. In contrast, ADX mice showed modest, tissue-specific increases in inflammatory gene expression, primarily in the liver and heart, suggesting limited regulation by physiological CORT levels. SF did not significantly increase pro-inflammatory gene expression compared with controls. In conclusion, CORT exerts potent, dose-dependent, and tissue-specific suppression of pro-inflammatory gene expression that is not modulated by acute SF in male mice.<\/jats:p>","DOI":"10.1242\/bio.062757","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:47:51Z","timestamp":1783522071000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological corticosterone suppresses pro-inflammatory cytokine gene expression in a tissue-dependent manner independent of sleep fragmentation in male mice"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6216-7200","authenticated-orcid":false,"given":"Hunter J.","family":"Weaver","sequence":"first","affiliation":[{"name":"Western Kentucky University Department of Biological Sciences , , Bowling Green, KY 42101 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Turner","sequence":"additional","affiliation":[{"name":"Western Kentucky University Department of Biological Sciences , , Bowling Green, KY 42101 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Thuan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Western Kentucky University Department of Biological Sciences , , Bowling Green, KY 42101 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9850-0681","authenticated-orcid":false,"given":"Noah T.","family":"Ashley","sequence":"additional","affiliation":[{"name":"Western Kentucky University Department of Biological Sciences , , Bowling Green, KY 42101 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"2026072805080483100_BIO062757C1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s00424-011-1044-0","article-title":"Sleep and immune function","volume":"463","author":"Besedovsky","year":"2012","journal-title":"Pfl\u00fcgers Arch."},{"key":"2026072805080483100_BIO062757C2","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nri.2017.1","article-title":"Immune regulation by glucocorticoids","volume":"17","author":"Cain","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"2026072805080483100_BIO062757C3","doi-asserted-by":"publisher","first-page":"eaar8590","DOI":"10.1126\/sciadv.aar8590","article-title":"Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans","volume":"4","author":"Cedernaes","year":"2018","journal-title":"Sci. Adv."},{"key":"2026072805080483100_BIO062757C4","doi-asserted-by":"publisher","first-page":"e216","DOI":"10.1371\/journal.pbio.0060216","article-title":"Is sleep essential?","volume":"6","author":"Cirelli","year":"2008","journal-title":"PLoS Biol."},{"key":"2026072805080483100_BIO062757C5","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1086\/701170","article-title":"Short-term sleep loss alters cytokine gene expression in brain and peripheral tissues and increases plasma corticosterone of zebra finch (","volume":"92","author":"Cooper","year":"2019","journal-title":"Physiol. Biochem. Zool."},{"key":"2026072805080483100_BIO062757C6","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.1007\/s40279-022-01706-y","article-title":"Effects of acute sleep loss on physical performance: a systematic and meta-analytical review","volume":"52","author":"Craven","year":"2022","journal-title":"Sports Med."},{"key":"2026072805080483100_BIO062757C7","doi-asserted-by":"publisher","first-page":"R1062","DOI":"10.1152\/ajpregu.00049.2015","article-title":"Acute sleep fragmentation induces tissue-specific changes in cytokine gene expression and increases serum corticosterone concentration","volume":"308","author":"Dumaine","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2026072805080483100_BIO062757C8","doi-asserted-by":"publisher","first-page":"E25","DOI":"10.1212\/01.wnl.0000164850.68115.81","article-title":"Cognitive benefits of sleep and their loss due to sleep deprivation","volume":"64","author":"Ellenbogen","year":"2005","journal-title":"Neurology"},{"key":"2026072805080483100_BIO062757C9","doi-asserted-by":"publisher","first-page":"14763","DOI":"10.1038\/s41598-022-19166-9","article-title":"Contrasting effects of sleep fragmentation and angiotensin-II treatment upon pro-inflammatory responses of mice","volume":"12","author":"Ensminger","year":"2022","journal-title":"Sci. Rep."},{"key":"2026072805080483100_BIO062757C10","doi-asserted-by":"publisher","first-page":"R374","DOI":"10.1152\/ajpregu.00565.2004","article-title":"Antioxidant defense responses to sleep loss and sleep recovery","volume":"288","author":"Everson","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2026072805080483100_BIO062757C11","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.smrv.2011.05.001","article-title":"Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery","volume":"16","author":"Faraut","year":"2012","journal-title":"Sleep Med. Rev."},{"key":"2026072805080483100_BIO062757C12","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1038\/s42003-021-02825-4","article-title":"Role of sleep deprivation in immune-related disease risk and outcomes","volume":"4","author":"Garbarino","year":"2021","journal-title":"Commun. Biol."},{"key":"2026072805080483100_BIO062757C13","first-page":"120","article-title":"Obstructive sleep apnea diagnosis and management","volume":"114","author":"Goyal","year":"2017","journal-title":"Mo. Med."},{"key":"2026072805080483100_BIO062757C14","doi-asserted-by":"publisher","first-page":"e17539","DOI":"10.7717\/peerj.17539","article-title":"Effect of glucocorticoid blockade on inflammatory responses to acute sleep fragmentation in male mice","volume":"12","author":"Hasan","year":"2024","journal-title":"PeerJ"},{"key":"2026072805080483100_BIO062757C15","doi-asserted-by":"publisher","first-page":"801341","DOI":"10.1155\/2013\/801341","article-title":"Sleep loss as a factor to induce cellular and molecular inflammatory variations","volume":"2013","author":"Hurtado-Alvarado","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"2026072805080483100_BIO062757C16","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1096\/fasebj.10.5.8621064","article-title":"Partial night sleep deprivation reduces natural killer and cellular immune responses in humans","volume":"10","author":"Irwin","year":"1996","journal-title":"FASEB J."},{"key":"2026072805080483100_BIO062757C17","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.biopsych.2015.05.014","article-title":"Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation","volume":"80","author":"Irwin","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"2026072805080483100_BIO062757C18","doi-asserted-by":"publisher","first-page":"i5210","DOI":"10.1136\/bmj.i5210","article-title":"Health consequences of shift work and insufficient sleep","volume":"355","author":"Kecklund","year":"2016","journal-title":"BMJ"},{"key":"2026072805080483100_BIO062757C19","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jsmc.2022.02.008","article-title":"The effects of insomnia and sleep loss on cardiovascular disease","volume":"17","author":"Khan","year":"2022","journal-title":"Sleep Med. Clin."},{"key":"2026072805080483100_BIO062757C20","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"2026072805080483100_BIO062757C21","doi-asserted-by":"publisher","first-page":"e14660","DOI":"10.14814\/phy2.14660","article-title":"The effect of acute sleep deprivation on skeletal muscle protein synthesis and the hormonal environment","volume":"9","author":"Lamon","year":"2021","journal-title":"Physiol. Rep."},{"key":"2026072805080483100_BIO062757C22","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1002\/alz.12930","article-title":"Acute sleep loss decreases CSF-to-blood clearance of Alzheimer's disease biomarkers","volume":"19","author":"Liu","year":"2023","journal-title":"Alzheimers Dement"},{"key":"2026072805080483100_BIO062757C23","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.smrv.2007.07.007","article-title":"Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity","volume":"12","author":"Meerlo","year":"2008","journal-title":"Sleep Med. Rev."},{"key":"2026072805080483100_BIO062757C24","doi-asserted-by":"publisher","first-page":"R781","DOI":"10.1152\/ajpregu.00358.2019","article-title":"Chemical sympathectomy reduces peripheral inflammatory responses to acute and chronic sleep fragmentation","volume":"318","author":"Mishra","year":"2020","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2026072805080483100_BIO062757C25","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.neuroscience.2022.09.022","article-title":"Peripheral sympathectomy alters neuroinflammatory and microglial responses to sleep fragmentation in female mice","volume":"505","author":"Mishra","year":"2022","journal-title":"Neuroscience"},{"key":"2026072805080483100_BIO062757C26","doi-asserted-by":"publisher","first-page":"C1","DOI":"10.1016\/0303-7207(92)90091-J","article-title":"The ups and downs of glucocorticoid physiology. Permissive and suppressive effects revisited","volume":"90","author":"Munck","year":"1992","journal-title":"Mol. Cell. Endocrinol."},{"key":"2026072805080483100_BIO062757C27","doi-asserted-by":"publisher","first-page":"6475","DOI":"10.1055\/s-0046-1820471","article-title":"Sleep fragmentation differentially modifies EEG delta power during slow wave sleep in socially isolated and paired mice","volume":"2","author":"Ramesh","year":"2009","journal-title":"Sleep Sci."},{"key":"2026072805080483100_BIO062757C28","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1210\/edrv.21.1.0389","article-title":"How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions","volume":"21","author":"Sapolsky","year":"2000","journal-title":"Endocr. Rev."},{"key":"2026072805080483100_BIO062757C29","doi-asserted-by":"publisher","first-page":"E11","DOI":"10.1152\/ajpendo.00100.2011","article-title":"Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function","volume":"301","author":"Taves","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2026072805080483100_BIO062757C30","doi-asserted-by":"publisher","first-page":"9360","DOI":"10.3390\/ijms21249360","article-title":"Light pollution and cancer","volume":"21","author":"Walker","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2026072805080483100_BIO062757C31","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.3390\/brainsci13101472","article-title":"Acute or chronic exposure to corticosterone promotes wakefulness in mice","volume":"13","author":"Yao","year":"2023","journal-title":"Brain Sci."},{"key":"2026072805080483100_BIO062757C32","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.neulet.2014.07.043","article-title":"Chronic sleep restriction elevates brain interleukin-1 beta and tumor necrosis factor-alpha and attenuates brain-derived neurotrophic factor expression","volume":"580","author":"Zielinski","year":"2014","journal-title":"Neurosci. Lett."}],"container-title":["Biology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062757\/3707515\/bio062757.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062757\/3710380\/bio062757.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062757\/3710380\/bio062757.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:08:12Z","timestamp":1785229692000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/bio\/article\/15\/7\/bio062757\/372403\/Pharmacological-corticosterone-suppresses-pro"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,15]]}},"URL":"https:\/\/doi.org\/10.1242\/bio.062757","relation":{},"ISSN":["2046-6390"],"issn-type":[{"value":"2046-6390","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"article-number":"bio062757"}}