{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:55:50Z","timestamp":1791291350454,"version":"4.3.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Sleep insufficiency has become a global public health challenge and is closely associated with the onset of mood and anxiety disorders. Neuroinflammation and oxidative stress are considered key pathological substrates underlying these conditions. Ouabain is a prototypical cardiotonic glycoside and an endogenous ligand of Na\n                      <jats:sup>+<\/jats:sup>\n                      \/K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase. In recent years, ouabain has been reported to exert anti\u2010inflammatory and neuroprotective effects; however, whether it can ameliorate sleep deprivation (SD)\u2010associated affective abnormalities remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using a 72\u2010h modified multiple\u2010platform SD model in male ICR mice, we investigated whether low\u2010dose ouabain administration (3 \u00b5g\/kg, i.p.) alleviates anxiety\u2010like behaviors, as assessed by the open field test, and mitigates hippocampal inflammatory (cytokine TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20104, and IL\u201010) and redox disturbances (T\u2010AOC, SOD, GPx, MDA, and CAT), as measured by ELISA. In parallel, PLX5622 and pathway\u2010specific modulators were employed to explore the potential mechanisms underlying the beneficial effects of ouabain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, SD reduced center zone time in the open field by 56.05% without changing locomotor activity, increased hippocampal TNF\u2010\u03b1, IL\u20101\u03b2, and MDA by 105.11%, 82.50%, and 89.82%, respectively, and decreased IL\u20104, IL\u201010, SOD, GPx, CAT, and T\u2010AOC by 54.28%, 47.22%, 44.96%, 51.95%, 52.14%, and 46.20%, respectively. Administration of low\u2010dose ouabain significantly reversed these changes. PLX5622\u2010mediated microglial depletion produced a partially similar protective profile, and pharmacological interference with Src\/p38 MAPK\/NF\u2010\u03baB\u2010associated signaling attenuated the effect of ouabain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Collectively, these findings suggest that low\u2010dose ouabain mitigates acute SD\u2010induced anxiety\u2010like behavior, at least in part by suppressing hippocampal neuroinflammation and oxidative stress, and identify a potential signaling axis for further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71629","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:50:12Z","timestamp":1784879412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ouabain Relieves Sleep Deprivation\u2013Induced Anxiety\u2010Like Behavior in Mice by Suppressing Hippocampal Neuroinflammation and Oxidative Stress"],"prefix":"10.1002","volume":"16","author":[{"given":"Hanxiao","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Dali University; Clinical Medical School, Health Science Center Dali University  Dali China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medical, Health Science Center Dali University  Dali China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1691567"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2026.1782734"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00010.2018"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106196"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2020.102159"},{"issue":"3","key":"e_1_2_13_7_1","first-page":"E413","article-title":"Ouabain Is Secreted by the Adrenal Gland in Awake Dogs","volume":"264","author":"Boulanger B. 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