title: Amino acid metabolic dysfunction revealed in the prefrontal cortex of a rat model of depression.
abstract: Major depressive disorder (MDD) is a debilitating mood disorder. However, the molecular mechanism(s) underlying depression remain largely unknown. Here, we applied a GC-MS-based metabonomic approach in the chronic unpredictable mild stress (CUMS) model, a well-established rodent model of depression, to investigate significant metabolic changes in the rat prefrontal cortex (PFC). Multivariate statistical analysis - including principal component analysis, partial least squares-discriminate analysis, and pair-wise orthogonal projections to latent structures discriminant - was applied to identify differential PFC metabolites between CUMS rats and healthy controls. As compared to healthy control rats, CUMS rats were characterized by lower levels of isoleucine and glycerol in combination with higher levels of N-acetylaspartate and β-alanine. These findings should provide insight into the pathophysiological mechanism(s) underlying MDD and preliminary leads relevant to diagnostic biomarker discovery for depression.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Yang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 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, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Tang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Rufang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China. Electronic address: pengxie58@21cn.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001522:Behavior, Animal; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D005990:Glycerol / Q000032:analysis; D007532:Isoleucine / Q000032:analysis; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D015091:beta-Alanine / Q000032:analysis
chemical_list: D000596:Amino Acids; D007532:Isoleucine; D015091:beta-Alanine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D005990:Glycerol
keywords: Chronic unpredictable mild stress, CUMS; Depression, Major depressive disorder, MDD; Metabonomic, metabolomic; Prefrontal cortex, PFC