title: Effects of mood stabilizers on oxidative stress-induced cell death signaling pathways in the brains of rats subjected to the ouabain-induced animal model of mania: Mood stabilizers exert protective effects against ouabain-induced activation of the cell death pathway.
abstract: The present study aimed to investigate the effects of mood stabilizers, specifically lithium (Li) and valproate (VPA), on mitochondrial superoxide, lipid peroxidation, and proteins involved in cell death signaling pathways in the brains of rats subjected to the ouabain-induced animal model of mania. Wistar rats received Li, VPA, or saline twice a day for 13 days. On the 7th day of treatment, the animals received a single intracerebroventricular injection of ouabain or aCSF. After the ICV injection, the treatment with mood stabilizers continued for 6 additional days. The locomotor activity of rats was measured using the open-field test. In addition, we analyzed oxidative stress parameters, specifically levels of phosphorylated p53 (pp53), BAX and Bcl-2 in the brain of rats by immunoblot. Li and VPA reversed ouabain-related hyperactivity. Ouabain decreased Bcl-2 levels and increased the oxidative stress parameters BAX and pp53 in the brains of rats. Li and VPA improved these ouabain-induced cellular dysfunctions; however, the effects of the mood stabilizers were dependent on the protein and brain region analyzed. These findings suggest that the Na(+)/K(+)-ATPase can be an important link between oxidative damage and the consequent reduction of neuronal and glial density, which are both observed in BD, and that Li and VPA exert protective effects against ouabain-induced activation of the apoptosis pathway.
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806000, Brazil. Electronic address: samiravalvassori@unesc.net.
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806000, Brazil.
authors.forename: Wilson R
authors.initials: WR
authors.lastname: Resende
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806000, Brazil.
authors.forename: Jéssica
authors.initials: J
authors.lastname: Lopes-Borges
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806000, Brazil.
authors.forename: Edemilson
authors.initials: E
authors.lastname: Mariot
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806000, Brazil.
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Dal-Pont
authors.affiliation: Laboratory of Exercise Biochemistry and Physiology, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Vitto
authors.affiliation: Laboratory of Exercise Biochemistry and Physiology, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Luz
authors.affiliation: Laboratory of Exercise Biochemistry and Physiology, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Claudio T
authors.initials: CT
authors.lastname: de Souza
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806000, Brazil; Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000633:toxicity*; D007276:Injections, Intraventricular; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D010042:Ouabain / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D018692:Antimanic Agents; D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D010042:Ouabain
keywords: Bax; Bcl-2; Bipolar disorder; Ouabain; Oxidative stress; P53