{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:02Z","timestamp":1787028482915,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of Taiwan","award":["108-2314-B-038-075-MY2"],"award-info":[{"award-number":["108-2314-B-038-075-MY2"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["110-2314-B-038-069"],"award-info":[{"award-number":["110-2314-B-038-069"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["111-2314-B-038-061"],"award-info":[{"award-number":["111-2314-B-038-061"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["111TMUH-MOST-03"],"award-info":[{"award-number":["111TMUH-MOST-03"]}]},{"name":"Taipei Medical University Hospital","award":["108-2314-B-038-075-MY2"],"award-info":[{"award-number":["108-2314-B-038-075-MY2"]}]},{"name":"Taipei Medical University Hospital","award":["110-2314-B-038-069"],"award-info":[{"award-number":["110-2314-B-038-069"]}]},{"name":"Taipei Medical University Hospital","award":["111-2314-B-038-061"],"award-info":[{"award-number":["111-2314-B-038-061"]}]},{"name":"Taipei Medical University Hospital","award":["111TMUH-MOST-03"],"award-info":[{"award-number":["111TMUH-MOST-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rapid eye movement (REM) sleep deprivation triggers mania and induces cardiac fibrosis. Beyond neuroprotection, lithium has cardioprotective potential and antifibrotic activity. This study investigated whether lithium improved REM sleep deprivation-induced cardiac dysfunction and evaluated the potential mechanisms. Transthoracic echocardiography, histopathological analysis, and Western blot analysis were performed in control and REM sleep-deprived rats with or without lithium treatment (LiCl of 1 mmol\/kg\/day administered by oral gavage for 4 weeks) in vivo and in isolated ventricular preparations. The results revealed that REM sleep-deprived rats exhibited impaired contractility and greater fibrosis than control and lithium-treated REM sleep-deprived rats. Western blot analysis showed that REM sleep-deprived hearts had higher expression levels of transforming growth factor beta (TGF-\u03b2), phosphorylated Smad 2\/3, and alpha-smooth muscle actin than lithium-treated REM sleep-deprived and control hearts. Moreover, lithium-treated REM sleep-deprived hearts had lower expression of angiotensin II type 1 receptor, phosphorylated nuclear factor kappa B p65, calcium release-activated calcium channel protein 1, transient receptor potential canonical (TRPC) 1, and TRPC3 than REM sleep-deprived hearts. The findings suggest that lithium attenuates REM sleep deprivation-induced cardiac fibrogenesis and dysfunction possibly through the downregulation of TGF-\u03b2, angiotensin II, and Ca2+ signaling.<\/jats:p>","DOI":"10.3390\/ijms231911226","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T23:13:27Z","timestamp":1664147607000},"page":"11226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Lithium Treatment Improves Cardiac Dysfunction in Rats Deprived of Rapid Eye Movement Sleep"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8454-7414","authenticated-orcid":false,"given":"Pao-Huan","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Psychiatry, Taipei Medical University Hospital, Taipei 11031, Taiwan"},{"name":"Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-4752","authenticated-orcid":false,"given":"Cheng-Chih","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuen-Hsin","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8687-5091","authenticated-orcid":false,"given":"Yu-Hsun","family":"Kao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7224-4491","authenticated-orcid":false,"given":"Yi-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.smrv.2016.06.007","article-title":"Chronotype and circadian rhythm in bipolar disorder: A systematic review","volume":"34","author":"Melo","year":"2017","journal-title":"Sleep Med. 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