title: Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats.
abstract: Bipolar Disorder (BD) is one of the most severe psychiatric disorders. Despite adequate treatment, patients continue to have recurrent mood episodes, residual symptoms, and functional impairment. Some preclinical studies have shown that histone deacetylase inhibitors may act on manic-like behaviors. Neurotrophins have been considered important mediators in the pathophysiology of BD. The present study aims to investigate the effects of lithium (Li), valproate (VPA), and sodium butyrate (SB), an HDAC inhibitor, on BDNF, NGF and GDNF in the brain of rats subjected to an animal model of mania induced by ouabain. Wistar rats received a single ICV injection of ouabain or artificial cerebrospinal fluid. From the day following ICV injection, the rats were treated for 6 days with intraperitoneal injections of saline, Li, VPA or SB twice a day. In the 7th day after ouabain injection, locomotor activity was measured using the open-field test. The BDNF, NGF and GDNF levels were measured in the hippocampus and frontal cortex by sandwich-ELISA. Li, VPA or SB treatments reversed ouabain-related manic-like behavior. Ouabain decreased BDNF, NGF and GDNF levels in hippocampus and frontal cortex of rats. The treatment with Li, VPA or SB reversed these impairment induced by ouabain. In addition, Li, VPA and SB per se increased NGF and GDNF levels in hippocampus of rats. Our data support the notion that neurotrophic factors play a role in BD and in the mechanisms of the action of Li, VPA and SB.
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: Roger B
authors.initials: RB
authors.lastname: Varela
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: 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: 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: Rafaela T
authors.initials: RT
authors.lastname: Amboni
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: Guilherme
authors.initials: G
authors.lastname: Bianchini
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: D000339:Affect / Q000187:drug effects; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D020148:Butyric Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology; D018020:Lithium Compounds / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020932:Nerve Growth Factor / Q000378:metabolism*; D010042:Ouabain / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006633:Histamine Antagonists; D018020:Lithium Compounds; D020148:Butyric Acid; D010042:Ouabain; D014635:Valproic Acid; D020932:Nerve Growth Factor
keywords: BDNF; Bipolar disorder; GDNF; Histone deacetylase; NGF; Ouabain