This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractDepression is a worldwide disability disease associated with high morbidity and has increased dramatically in the last few years. The differential diagnosis and the definition of an individualized therapy for Depression is hampered by the absence of specific biomarkers. The aim of this study was to evaluate the phospholipdiomic profile of brain and myocardium in a mouse model of depression induced by chronic unpredictable stress. The lipidomic profile was evaluated by thin layer and liquid chromatography and mass spectrometry and lipid oxidation was estimated by FOX II assay. Antioxidant enzymes activity and the GSH/GSSG ratio were also evaluated.Results showed that chronic stress affect primarily the lipid profile of the brain, inducing an increased in lipid hydroperoxides, which was not detected in the myocardium. A significant decrease in phospahtidylinositol (PI) and in cardiolipin (CL) relative contents and also oxidation of cardiolipin and significant increase of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were observed in in brain from mice after unpredictable chronic stress conditions. In myocardium only an increase in PC content was observed. Nevertheless, both organs present a decreased GSH/GSSG ratio when compared to control groups, corroborating the occurrence of oxidative stress. The enzyme activities CAT and SOD were found to be decreased in the myocardium and increased in the brain, while glutathione reductase (GR) was decreased in brain. Our results indicate that in a mouse model for studying depression induced by chronic unpredictable stress, the modification of the expression of oxidative stress related enzymes did not prevent lipid oxidation in organs, particularly in the brain. These observations suggest that depression has an impact in the brain lipidome and that further studies are needed to better understand lipid role in depression and to evaluate their potential as future biomarkers.3

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