title: Olfactory bulbectomy in mice triggers transient and long-lasting behavioral impairments and biochemical hippocampal disturbances.
abstract: Major depressive disorder (MDD) is a neuropsychiatric disease that is associated with profound disturbances in affected individuals. Elucidating the pathophysiology of MDD has been frustratingly slow, especially concerning the neurochemical events and brain regions associated with disease progression. Thus, we evaluated the time-course (up to 8weeks) behavioral and biochemical effects in mice that underwent to a bilateral olfactory bulbectomy (OBX), which is used to modeling depressive-like behavior in rodents. Similar to the symptoms in patients with MDD, OBX induced long-lasting (e.g., impairment of habituation to novelty, hyperactivity and an anxiety-like phenotype) and transient (e.g., loss of self-care and motivational behavior) behavioral effects. Moreover, OBX temporarily impaired hippocampal synaptosomal mitochondria, in a manner that would be associated with hippocampal-related synaptotoxicity. Finally, long-lasting pro-oxidative (i.e., increased levels of reactive oxygen species and nitric oxide and decreased glutathione levels) and pro-inflammatory (i.e., increased levels of pro-inflammatory cytokines IL-1, IL-6, TNF-α and decreased anti-inflammatory cytokine IL-10 levels) effects were induced in the hippocampus by OBX. Additionally, these parameters were transiently affected in the posterior and frontal cortices. This study is the first to suggest that the transient and long-lasting behavioral effects from OBX strongly correlate with mitochondrial, oxidative and inflammatory parameters in the hippocampus; furthermore, these effects show a weak correlation with these parameters in the cortex. Our findings highlight the underlying mechanisms involved in the biochemical time course of events related to depressive behavior.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: almeida_rf@yahoo.com.br.
authors.forename: Roberto Farina de
authors.initials: RF
authors.lastname: Almeida
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Max Planck Institute for Biophysical Chemistry, Neurobiology Department, Göttingen, Germany. Electronic address: ganzellam@gmail.com.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ganzella
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: dguilhermano@yahoo.com.br.
authors.forename: Daniele Guilhermano
authors.initials: DG
authors.lastname: Machado
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: emaildasamanta@yahoo.com.br.
authors.forename: Samanta Oliveira
authors.initials: SO
authors.lastname: Loureiro
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: douglasleffa@hotmail.com.
authors.forename: Douglas
authors.initials: D
authors.lastname: Leffa
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: andrequincozes@ufrgs.br.
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: leticiapettenuzzo@gmail.com.
authors.forename: Letícia Ferreira
authors.initials: LF
authors.lastname: Pettenuzzo
authors.affiliation: Departamento de Ciências da Saúde, Universidade Luterana do Brasil - Campus Santa Maria, RS, Brazil. Electronic address: duartmm@hotmail.com.
authors.forename: Marta Maria Medeiros Frescura
authors.initials: MMMF
authors.lastname: Duarte
authors.affiliation: Departamento de Ciências da Saúde, Universidade Luterana do Brasil - Campus Santa Maria, RS, Brazil. Electronic address: duartethiago89@yahoo.com.br.
authors.forename: Thiago
authors.initials: T
authors.lastname: Duarte
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: diogo@ufrgs.br.
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003865:Major Depressive Disorder / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000601:surgery*
keywords: Major depressive disorder; Mitochondrial; Olfactory bulbectomy; Open field test; Synaptosome preparation