title: Quantitative proteomics analysis of the liver reveals immune regulation and lipid metabolism dysregulation in a mouse model of depression.
abstract: 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. 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. 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 NFκB 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. 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.
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: You
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Tang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Rao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liao
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Inner Mongolia Autonomous Region people's Hospital, Hohhot, Inner Mongolia 010017, China.
authors.forename: Zihong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. Electronic address: xiepeng@cqmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D059445:Anhedonia / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002853:Chromatography, Liquid; D003866:Depressive Disorder / Q000378:metabolism*; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D008099:Liver / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D020543:Proteome; D040901:Proteomics; D011897:Random Allocation; D013315:Stress, Psychological / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D035501:Uncertainty
chemical_list: D019422:Dietary Sucrose; D020543:Proteome
keywords: Chronic unpredictable mild stress; Liver; Major depressive disorder; Proteomics; iTRAQ