title: The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression.
abstract: Major depressive disorder, with serious impairment in cognitive and social functioning, is a complex psychiatric disorder characterized by pervasive and persistent low mood and a loss of interest or pleasure. However, the underlying molecular mechanisms of depression remain largely unknown. In this study, we used a non-targeted metabolomics approach based on gas chromatography-mass spectrometry of the prefrontal cortex in chronic restraint stress (CRS)-treated rats. CRS was induced in the stress group by restraining rats in a plastic restrainer for 6h every day. This stress paradigm continued for 21 days. Body weight measurement and behavior tests were applied, including the sucrose preference test for anhedonia, the forced swimming test for despair-like behavior, and open field test and the elevated plus-maze to test for anxiety-like behaviors in rats after CRS. Differentially expressed metabolites associated with CRS-treated rats were identified by combining multivariate and univariate statistical analysis and corrected for multiple testing using the Benjamini-Hochberg procedure. A heat map of differential metabolites was constructed using Matlab. Ingenuity Pathways Analysis was applied to identify the predicted pathways and biological functions relevant to the bio-molecules of interest. Our findings showed that CRS induces depression-like behaviors and not anxiety-like behaviors. Thirty-six metabolites were identified as potential depression biomarkers involved in amino acid metabolism, energy metabolism and lipid metabolism, as well as a disturbance in neurotransmitters. Consequently, this study provides useful insights into the molecular mechanisms of depression.
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Lanxiang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Juncai
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. Electronic address: xiepeng973@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D001928:Brain Diseases, Metabolic / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D003863:Depression / Q000150:complications* / Q000209:etiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005518:Food Preferences; D008401:Gas Chromatography-Mass Spectrometry; D008124:Locomotion / Q000502:physiology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology; D017397:Prefrontal Cortex / Q000378:metabolism*; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000009:adverse effects*; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D013395:Sucrose
keywords: Chronic restraint stress; Depression; Gas chromatography–mass spectrometry; Metabolomics; Rat