ITRAQ-based Quantitative Proteomics Analysis Of The Liver In A Mouse Model Of Depression

Background Major depressive disorder(MDD)is a highly prevalent and debilitating mental illness with substantial impairments in quality of life and functioning.However,the pathophysiology of major depression remains poorly understood.Combining the brain and body should provide a comprehensive understanding of the etiology of MDD.As the largest internal organ of the human body,the liver has an important function,yet no proteomic study has assessed liver protein expression in a preclinical model of depression.Objective Using the chronic unpredictable mild stress(CUMS)mouse model of depression,differential protein expression between CUMS and control(CON)mice was examined in the liver proteome using isobaric tag for relative and absolute quantitation(iTRAQ)coupled with tandem mass spectrometry.MethodsAfter acclimatization and 1 week of training(for the sucrose preference test),forty healthy adult male C57BL/6J mice(8–10 weeks of age)were randomly sorted into groups of 20 mice.Next,CUMS mice were subjected to various and repeated unpredictable mild stressors for a period of 1 week(sub-CUMS)and 4weeks(CUMS).After evaluate of the CUMS mouse model,we selected 10 mice liver each group for iTRAQ labeling and other 6:6 for Western blotting.Results More than 4000 proteins were identified and 66 most significantly differentiated proteins were used for further bioinformatic analysis.According to the ingenuity pathway analysis(IPA),we found that proteins related to the inflammation response,immune regulation,lipid metabolism and NF?B signaling network were altered by CUMS.Moreover,four proteins closely associated with these processes,hemopexin,haptoglobin,cytochrome P450 2A4(CYP2A4)and bile salt sulfotransferase 1(SULT2A1),were validated by western blotting.Conclusion In conclusion,we report,for the first time,the liver protein expression profile in the CUMS mouse model of depression.Our findings provide novel insight(liver–brain axis)into the multifaceted mechanisms of major depressive disorder.