{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T22:59:33Z","timestamp":1772665173687,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2059\/22"],"award-info":[{"award-number":["2059\/22"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bipolar disorder (BD) is a severe and common chronic mental illness characterized by recurrent mood swings between depression and mania. The biological basis of the disease is poorly understood, and its treatment is unsatisfactory. Na+, K+-ATPase is a major plasma membrane transporter and signal transducer. The catalytic \u03b1 subunit of this enzyme is the binding site for cardiac steroids. Three \u03b1 isoforms of the Na+, K+-ATPase are present in the brain. Previous studies have supported the involvement of the Na+, K+-ATPase and endogenous cardiac steroids (ECS) in the etiology of BD. Decreased brain ECS has been found to elicit anti-manic and anti-depressive-like behaviors in mice and rats. However, the identity of the specific \u03b1 isoform involved in these behavioral effects is unknown. Here, we demonstrated that decreasing ECS through intracerebroventricular (i.c.v.) administration of anti-ouabain antibodies (anti-Ou-Ab) decreased the activity of \u03b11+\/\u2212 mice in forced swimming tests but did not change the activity in wild type (wt) mice. This treatment also affected exploratory and anxiety behaviors in \u03b11+\/\u2212 but not wt mice, as measured in open field tests. The i.c.v. administration of anti-Ou-Ab decreased brain ECS and increased brain Na+, K+-ATPase activity in wt and \u03b11+\/\u2212 mice. The serum ECS was lower in \u03b11+\/\u2212 than wt mice. In addition, a study in human participants demonstrated that serum ECS significantly decreased after treatment. These results suggest that the Na+, K+-ATPase \u03b11 isoform is involved in depressive- and manic-like behaviors and support that the Na+, K+-ATPase\/ECS system participates in the etiology of BD.<\/jats:p>","DOI":"10.3390\/ijms25031644","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:11:27Z","timestamp":1706515887000},"page":"1644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Involvement of the Na+, K+-ATPase \u03b11 Isoform and Endogenous Cardiac Steroids in Depression- and Manic-like Behaviors"],"prefix":"10.3390","volume":"25","author":[{"given":"Noa","family":"Horesh","sequence":"first","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilana","family":"Pelov","sequence":"additional","affiliation":[{"name":"Jerusalem Mental Health Center, Eitanim Psychiatric Hospital, Jerusalem 91060, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilana","family":"Pogodin","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiba","family":"Zannadeh","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haim","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasiia Leonidovna","family":"Mikhrina","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5597-6455","authenticated-orcid":false,"given":"Moran","family":"Dvela-Levitt","sequence":"additional","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishnu Priya","family":"Sampath","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7042-4648","authenticated-orcid":false,"given":"David","family":"Lichtstein","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/sj.mp.4002151","article-title":"Whole-genome association study of bipolar disorder","volume":"13","author":"Sklar","year":"2008","journal-title":"Mol. 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