title: Potential antidepressant and resilience mechanism revealed by metabolomic study on peripheral blood mononuclear cells of stress resilient rats.
abstract: Resilience is an active coping response to stress, which plays a very important role in major depressive disorder study. The molecular mechanisms underlying such resilience are poorly understood. Peripheral blood mononuclear cells (PBMCs) were promising objects in unveiling the underlying pathogenesis of resilience. Hereby we carried out successive study on PBMCs metabolomics in resilient rats of chronic unpredictable mild stress (CUMS) model. A gas chromatography-mass spectrometry (GC-MS) metabolomic approach coupled with principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to detect differential metabolites in PBMCs of resilient rats. Ingenuity Pathways Analysis (IPA) was applied for pathway analysis. A set of differential metabolites including Malic acid, Ornithine, l-Lysine, Stigmasterol, Oleic acid, γ-Tocopherol, Adenosine and N-acetyl-d-glucosamine were significantly altered in resilient rats, meanwhile promoting antidepressant research. As revealed by IPA that aberrant energy metabolism, HIFα signaling, neurotransmitter, O-GlcNAcylation and cAMP signaling cascade in peripheral might be evolved in the pathogenesis of coping mechanism. The GC-MS based metabolomics may contribute to better understanding of resilience, as well as shedding light on antidepressant discovery.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Shu-Xiao
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, 400016 Chongqing, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, 400016 Chongqing, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Rao
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: De-Yu
authors.initials: DY
authors.lastname: Yang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, 400016 Chongqing, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: De-Zhi
authors.initials: DZ
authors.lastname: Zou
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Zhao
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, 400016 Chongqing, China; School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, 400016 Chongqing, China. Electronic address: xiepeng@cqmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D001835:Body Weight / Q000502:physiology; D002952:Citric Acid Cycle / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D016002:Discriminant Analysis; D004195:Disease Models, Animal; D005518:Food Preferences / Q000523:psychology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D055500:Resilience, Psychological; D015398:Signal Transduction / Q000502:physiology; D013315:Stress, Psychological / Q000473:pathology* / Q000523:psychology*
chemical_list: D000928:Antidepressive Agents; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000242:Cyclic AMP
keywords: Chronic unpredictable mild stress (CUMS); Gas chromatography–mass spectrometry (GC–MS); Metabolomics; Peripheral blood mononuclear cells (PBMC); Resilience