title: Depressive-like behavior induced by tumor necrosis factor-α is attenuated by m-trifluoromethyl-diphenyl diselenide in mice.
abstract: A growing body of evidence associates activation of immune system with depressive symptoms. Accordingly, pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), have been shown to play a pivotal role in the pathophysiology of depression. The aim of this study was to evaluate the effectiveness of acute and subchronic treatments with (m-CF3-PhSe)2 to prevent the depressive-like behavior induced by intracerebroventricular injection of TNF-α in mice. TNF-α induced depressive-like behavior in the forced swimming test (FST) and tail suspension test (TST) (0.1 and 0.001 ƒg/5 μL/site, respectively) without changing locomotor activity, performed in the locomotor activity monitor (LAM). Acute (0.01-50 mg/kg; intragastric (i.g.); 30 min) and subchronic (0.01 and 0.1 mg/kg; i.g.; 14 days) treatments with (m-CF3-PhSe)2 at low doses were effective against the effect of TNF-α in the FST and TST. Nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK), important proteins in TNF-activated signaling, were determined in the prefrontal cortex and hippocampus of mouse. TNF-α (0.1 ƒg/5 μL/site) increased NF-κB levels and p38 MAPK activation in both brain areas and acute (10 mg/kg; i.g.) and subchronic (0.01 mg/kg; i.g.) treatments with (m-CF3-PhSe)2 were effective in attenuating this increase. Although more studies are necessary to indicate this compound as a therapeutic alternative to depression, the antidepressant-like and anti-inflammatory effects of (m-CF3-PhSe)2 demonstrated herein may support it as an interesting molecule in the search for new drugs to treat depressive disorders that have been largely linked to immune process and inflammation.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: César Augusto
authors.initials: CA
authors.lastname: Brüning
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Franciele
authors.initials: F
authors.lastname: Martini
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Suelen Mendonça
authors.initials: SM
authors.lastname: Soares
authors.affiliation: Grupo de Pesquisa em Neurobiotecnologia - GPN, CDTec, Unidade Biotecnologia, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil.
authors.forename: Lucielli
authors.initials: L
authors.lastname: Savegnago
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Tuane Bazanella
authors.initials: TB
authors.lastname: Sampaio
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil. Electronic address: criswn@ufsm.br.
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D017646:Organosilicon Compounds / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D016328:NF-kappa B; D017646:Organosilicon Compounds; D014409:Tumor Necrosis Factor-alpha; C546861:m-trifluoromethyl-diphenyl diselenide; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Depression; NF-κB; Selenium; TNF-α; p38 MAPK