Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 76, Issue -, Pages 1-11Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2017.02.013
Keywords
Major depressive disorder; Olfactory bulbectomy; Open field test; Mitochondrial; Synaptosome preparation
Funding
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [2037/2017]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [440763/2016-9]
- Instituto Nacional de Ciencia e Tecnologia (INCT) para Excitotoxicidade e Neuroprotecao [465671/2014-4]
- PRONEX from Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
- Financiadora de Estudos e Projetos (FINEP) research grant BRede Instituto Brasileiro de Neurociencias (IBN-Net) [01.06.0842-00]
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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 8 weeks) 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-alpha 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. (C) 2017 Elsevier Inc. All rights reserved.
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