{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:46:38Z","timestamp":1778769998877,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sleep, a core circadian rhythm, maintains physiological homeostasis. Its dysfunction links to neuropsychiatric disorders. Clinically, poor sleep impairs positive emotions and enhances negative emotion susceptibility, but the mechanism remains unclear, potentially involving circadian clock genes and neuroinflammatory pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Divide the male C57BL\/6J mice into the following five groups: Non-sleep deprivation (SD) control (CON), sleep recovery 14-day after SD 7-day (SD7R14), sleep recovery 21-day after SD 7-day (SD7R21), sleep recovery 14-day after SD 14-day (SD14R14), and sleep recovery 21-day after SD 14-day (SD14R21). Behavioral tests evaluated anxiety-like behaviors, fear and andanhedonia. Histological staining observed neuronal morphology in the medial prefrontal cortex (mPFC), and RT-qPCR was employed to measure mRNA levels of circadian clock genes, Silent information regulator 6 (\n                      <jats:italic>Sirt6<\/jats:italic>\n                      ), High mobility group box-1 (\n                      <jats:italic>Hmgb1<\/jats:italic>\n                      ), and inflammatory factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SD induces time-dependent anxiety-like behaviors (reduced exploratory activity in elevated mazes), anhedonia (decreased sucrose preference), and fear behaviors (prolonged immobility in forced swim and tail suspension tests). Histological analysis reveals reversible neuronal damage in the mPFC, with complete recovery observed after 21\u202fdays of sleep restitution. Molecular analyses show dysregulation of the muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (\n                      <jats:italic>Bmal1<\/jats:italic>\n                      ) and circadian locomotor output cycles kaput (\n                      <jats:italic>Clock<\/jats:italic>\n                      ) circadian pathway and activation of the Sirt6\/Hmgb1 inflammatory axis, leading to proinflammatory cytokine release (\n                      <jats:italic>TNF\u03b1, IL1\u03b2, COX-2, IL6<\/jats:italic>\n                      ), with partial recovery after sleep restoration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SD for 7-day or 14-day may impair emotional behaviors by disrupting the RNA expression of clock genes and the Sirt6\/Hmgb1 inflammatory axis, while sleep recovery for 14-day or 21-day can partially reverse this impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2025.1742898","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T06:32:20Z","timestamp":1768285940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Dynamic effects of sleep deprivation on emotional behavior, circadian rhythm genes, and inflammatory infiltration in the medial prefrontal cortex"],"prefix":"10.3389","volume":"19","author":[{"given":"Dandan","family":"Cao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Geng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoqiong","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"zsaa271","DOI":"10.1093\/sleep\/zsaa271","article-title":"Immunization with a heat-killed bacterium, Mycobacterium vaccae NCTC 11659, prevents the development of cortical hyperarousal and a PTSD-like sleep phenotype after sleep disruption and acute stress in mic","volume":"44","author":"Bowers","year":"2021","journal-title":"Sleep"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/mp.2014.138","article-title":"Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder","volume":"20","author":"Bunney","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1083\/jcb.201603076","article-title":"The circadian coordination of cell biology","volume":"215","author":"Chaix","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s12276-022-00736-w","article-title":"The mechanism of HMGB1 secretion and release","volume":"54","author":"Chen","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"104944","DOI":"10.1016\/j.neuint.2020.104944","article-title":"Microglia dynamics in sleep\/wake states and in response to sleep loss","volume":"143","author":"Deurveilher","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41392-022-00899-y","article-title":"Molecular regulations of circadian rhythm and implications for physiology and diseases","volume":"7","author":"Fagiani","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2889","DOI":"10.3389\/fimmu.2018.02889","article-title":"Neuroprotective effects of Ginsenoside-Rg1 against depression-like behaviors via suppressing glial activation, synaptic deficits, and neuronal apoptosis in rats","volume":"9","author":"Fan","year":"2018","journal-title":"Front. Immunol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1007\/s11920-014-0500-x","article-title":"The interplay between sleep and emotion regulation: conceptual framework empirical evidence and future directions","volume":"16","author":"Gruber","year":"2014","journal-title":"Curr. Psychiatry Rep."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.14336\/AD.2022.0413","article-title":"SIRT6 in aging, metabolism, inflammation and cardiovascular diseases","volume":"13","author":"Guo","year":"2022","journal-title":"Aging Dis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.3390\/ijms20051223","article-title":"Aging, melatonin, and the pro- and anti-inflammatory networks","volume":"20","author":"Hardeland","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"7819","DOI":"10.1038\/s41467-025-63131-9","article-title":"Prefrontal cortex astrocytes modulate distinct neuronal populations to control anxiety-like behavior","volume":"16","author":"Kim","year":"2025","journal-title":"Nat. Commun."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1126\/science.1226339","article-title":"Transcriptional architecture and chromatin landscape of the core circadian clock in mammals","volume":"338","author":"Koike","year":"2012","journal-title":"Science"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1080\/15384047.2019.1702397","article-title":"SIRT6-PARP1 is involved in HMGB1 polyADP-ribosylation and acetylation and promotes chemotherapy-induced autophagy in leukemia","volume":"21","author":"Kong","year":"2020","journal-title":"Cancer Biol. Ther."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.tibs.2013.12.002","article-title":"Chromatin and beyond: the multitasking roles for SIRT6","volume":"39","author":"Kugel","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"158","DOI":"10.2174\/1570159X19666210609160017","article-title":"Understanding the role of histone deacetylase and their inhibitors in neurodegenerative disorders: current targets and future perspective","volume":"20","author":"Kumar","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"105779","DOI":"10.1016\/j.intimp.2019.105779","article-title":"SIRT1-regulated HMGB1 release is partially involved in TLR4 signal transduction: a possible anti-neuroinflammatory mechanism of resveratrol in neonatal hypoxic-ischemic brain injury","volume":"75","author":"Le","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e1001442","DOI":"10.1371\/journal.pbio.1001442","article-title":"Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles","volume":"10","author":"Le Martelot","year":"2012","journal-title":"PLoS Biol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1007\/s12264-021-00767-9","article-title":"Modulation of predator Cue-evoked tonic immobility by acetylcholine released in the basolateral complex of the amygdala","volume":"37","author":"Liu","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1097\/MIB.0000000000001265","article-title":"Bidirectional regulation of circadian disturbance and inflammation in inflammatory bowel disease","volume":"23","author":"Liu","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"20090","DOI":"10.1073\/pnas.0710131104","article-title":"Homer1a is a core brain molecular correlate of sleep loss","volume":"104","author":"Maret","year":"2007","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1097\/FBP.0000000000000844","article-title":"Antidepressant effect or bias? Systematic review and meta-analysis of studies using the forced swimming test","volume":"36","author":"Martins","year":"2025","journal-title":"Behav. Pharmacol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.cell.2014.06.050","article-title":"Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism","volume":"158","author":"Masri","year":"2014","journal-title":"Cell"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jad.2017.10.039","article-title":"Outdoor light at night and the prevalence of depressive symptoms and suicidal behaviors: a cross-sectional study in a nationally representative sample of Korean adults","volume":"227","author":"Min","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.bbi.2023.12.031","article-title":"Differential effects of sleep deprivation on behavior and microglia in a brain-region-specific manner in young and aged male mice","volume":"117","author":"Ni","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1037\/bul0000410","article-title":"Sleep loss and emotion: a systematic review and meta-analysis of over 50 years of experimental research","volume":"150","author":"Palmer","year":"2024","journal-title":"Psychol. Bull."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41580-019-0179-2","article-title":"Molecular mechanisms and physiological importance of circadian rhythms","volume":"21","author":"Patke","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"13771","DOI":"10.1073\/pnas.2000258117","article-title":"Vulnerability to helpless behavior is regulated by the circadian clock component CRYPTOCHROME in the mouse nucleus accumbens","volume":"117","author":"Porcu","year":"2020","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.euroneuro.2023.08.496","article-title":"Sucrose preference test: a systematic review of protocols for the assessment of anhedonia in rodents","volume":"77","author":"Primo","year":"2023","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"7257","DOI":"10.1038\/s41467-024-51716-9","article-title":"Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice","volume":"15","author":"Sarrazin","year":"2024","journal-title":"Nat. Commun."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.cmet.2019.02.014","article-title":"LINE1 derepression in aged wild-type and SIRT6-deficient mice drives inflammation","volume":"29","author":"Simon","year":"2019","journal-title":"Cell Metab."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1161\/ATVBAHA.117.309374","article-title":"Circadian control of inflammatory processes in atherosclerosis and its complications","volume":"37","author":"Steffens","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e0256983","DOI":"10.1371\/journal.pone.0256983","article-title":"Total sleep deprivation reduces top-down regulation of emotion without altering bottom-up affective processing","volume":"16","author":"Stenson","year":"2021","journal-title":"PLoS One"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.bbrc.2019.01.143","article-title":"Sirt6 deacetylase activity regulates circadian rhythms via Per2","volume":"511","author":"Sun","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e3003173","DOI":"10.1371\/journal.pbio.3003173","article-title":"Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythms and sleep","volume":"23","author":"Sun","year":"2025","journal-title":"PLoS Biol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1089\/jir.1998.18.793","article-title":"Sleep-associated changes in interleukin-1\u03b2 mRNA in the brain","volume":"18","author":"Taishi","year":"1998","journal-title":"J. Interf. Cytokine Res."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.bbi.2020.06.019","article-title":"Minocycline prevents the depressive-like behavior through inhibiting the release of HMGB1 from microglia and neurons","volume":"88","author":"Wang","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"7193","DOI":"10.1523\/JNEUROSCI.1150-08.2008","article-title":"Sleep deprivation effects on circadian clock gene expression in the cerebral cortex parallel electroencephalographic differences among mouse strains","volume":"28","author":"Wisor","year":"2008","journal-title":"J. Neurosci."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"5224","DOI":"10.1111\/bph.15261","article-title":"Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1\/TLR4\/NF-\u03baB and TNF-\u03b1\/TNFR1\/NF-\u03baB pathways","volume":"177","author":"Xu","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"20220712","DOI":"10.1515\/biol-2022-0712","article-title":"Circadian cycle and neuroinflammation","volume":"18","author":"Xu","year":"2023","journal-title":"Open Life Sci."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"52587","DOI":"10.3791\/52587","article-title":"The forced swim test as a model of depressive-like behavior","volume":"97","author":"Yankelevitch-Yahav","year":"2015","journal-title":"J Vis Exp"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1101\/gad.249417.114","article-title":"Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and period proteins in the mammalian circadian clock","volume":"28","author":"Ye","year":"2014","journal-title":"Genes Dev."}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2025.1742898\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T06:32:23Z","timestamp":1768285943000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2025.1742898\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":41,"alternative-id":["10.3389\/fnbeh.2025.1742898"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2025.1742898","relation":{},"ISSN":["1662-5153"],"issn-type":[{"value":"1662-5153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"article-number":"1742898"}}