{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:15:17Z","timestamp":1789434917448,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004935","name":"S\u00fcleyman Demirel \u00dcniversitesi","doi-asserted-by":"publisher","award":["TTU\u20102023\u20109098"],"award-info":[{"award-number":["TTU\u20102023\u20109098"]}],"id":[{"id":"10.13039\/501100004935","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bipolar disease (BD) has been strongly associated with the etiologies of mitochondrial reactive oxygen species (mROS), apoptosis, and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx. With the exception of BD, a number of neurological disorders have been linked to apoptosis and neuronal death mediated by mROS\u2010dependent activated TRPM2 channel stimulation. Lamotrigine (LMT), lithium (Li), and valproic acid (VPA) are mood stabilizers in BD, and they have strong antioxidant roles. However, the molecular mechanisms underlying LMT, Li, and VPA neuroprotection through TRPM2 channel inhibiton remain elusive in BD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>We evaluated the protective actions of LMT, Li, and VPA on BD (ouabain, OUA)\u2010induced oxidative neurotoxicity in SH\u2010SY5Y neuronal cells by modulating TRPM2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The SH\u2010SY5Y cells were divided into nine groups as follows: control, Li, VPA, LMT, OUA, OUA\u2009+\u2009Li, OUA\u2009+\u2009VPA, LMT\u2009+\u2009VPA, and OUA\u2009+\u2009TRPM2 antagonists (N\u2010(p\u2010amylcinnamoyl)anthranilic acid or carvacrol).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OUA exposure and TRPM2 agonist (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      and ADP\u2010ribose)\u2010induced TRPM2 stimulation and TRPM2 current densities were downregulated by the treatments of TRPM2 antagonist, Li, VPA, and LMT. The OUA\u2010induced upregulations of mROS, cytosolic ROS, lipid peroxidation, mitochondrial membrane dysfunction, apoptosis, Zn\n                      <jats:sup>2+<\/jats:sup>\n                      , cell death, and caspase\u20103, \u20108, and \u20109 values were also downregulated through the increases of cell viability, glutathione, and glutathione peroxidase by the treatments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The treatments of Li, VPA, and LMT modulate OUA\u2010mediated mROS, apoptosis, Zn\n                      <jats:sup>2+<\/jats:sup>\n                      , glutathione, and TRPM2\u2010mediated excess Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx. This could potentially offer protection against BD linked to elevated levels of mROS, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      , and Zn\n                      <jats:sup>2+<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bdi.70053","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T06:36:36Z","timestamp":1758263796000},"page":"483-500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mood Stabilizers (Lamotrigine, Lithium, and Valproic Acid) Decrease Bipolar Disease Model (Ouabain)\u2010Induced Oxidative Stress and Apoptosis Through the Inhibition of the TRPM2 Channel in Neuronal Cells"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-9532","authenticated-orcid":false,"given":"Esra Nur","family":"Kaplan","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine Suleyman Demirel University  Isparta T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1626-7810","authenticated-orcid":false,"given":"\u0130brahim","family":"Eren","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine Suleyman Demirel University  Isparta T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0887-6974","authenticated-orcid":false,"given":"Mustafa","family":"Naz\u0131ro\u011flu","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center Suleyman Demirel University  Isparta T\u00fcrkiye"},{"name":"Drug Discovery Unit BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry and Trade LTD  Isparta T\u00fcrkiye"},{"name":"Department of Biophysics Faculty of Medicine, 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