Li Juan, Tang Ge, Cheng Ke, Yang Deyu, Chen Guanghui, Liu Zhao, Zhang Rufang, Zhou Jingjing, Fang Liang, Fang Zheng, Du Xiangyu, Xie Peng
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China.
Mol Biosyst. 2014 Nov;10(11):2994-3001. doi: 10.1039/c4mb00388h.
Major depressive disorder (MDD) is a debilitating mood disorder with various etiopathological hypotheses. However the pathogenesis and diagnosis are still unclear. Peripheral blood mononuclear cells (PBMCs) have been shown to be well-suited to biomarker investigation in major depressive disorder (MDD), as well as to unveil the underlying pathogenesis of MDD. In this study, PBMCs were obtained from a chronic unpredictable mild stress (CUMS) rodent model of depression. A gas chromatography-mass spectrometry (GC/MS) metabolomic approach coupled with principal component analysis (PCA) and open partial least-squares discriminant analysis (OPLS-DA) statistical analysis was used to detect differential metabolites in PBMCs of depressed rats. A total number of 18 differential metabolites were screened out. Seven metabolites showed lower levels in CUMS relative to healthy control rats, including aspartic acid, glutamic acid, dehydroascorbic acid, aminomalonic acid, glycine, β-alanine, and ethanolamine, while eleven metabolites showed an increase in CUMS relative to healthy control rats, namely erythronic acid, fructose, β-tocopherol, adenosine-5-monophosphate, 5-hydroxytryptamine, 5-hydroxytryptamine, glycolic acid, α-tocopherol, tetradecanoic acid, creatinine, 4,5-dimethyl-2,6-dihydroxypyrimidine, and myo-inositol. These molecular changes were closely related to perturbations in neurotransmitter metabolism, energy metabolism and oxidative stress metabolism. Biochemical function analysis of these differential metabolites suggested that altered neurotransmitter, energy and oxidative metabolism disorder might be evolved in the pathogenesis of MDD, which could be of valuable assistance in the clinical diagnosis of MDD.
重度抑郁症（MDD）是一种使人衰弱的情绪障碍，存在多种病因病理假说。然而，其发病机制和诊断仍不明确。外周血单核细胞（PBMCs）已被证明非常适合用于重度抑郁症（MDD）的生物标志物研究，以及揭示MDD的潜在发病机制。在本研究中，从慢性不可预测轻度应激（CUMS）抑郁症啮齿动物模型中获取PBMCs。采用气相色谱 - 质谱联用（GC/MS）代谢组学方法，结合主成分分析（PCA）和开放式偏最小二乘判别分析（OPLS - DA）统计分析，来检测抑郁大鼠PBMCs中的差异代谢物。共筛选出18种差异代谢物。相对于健康对照大鼠，有7种代谢物在CUMS组中水平较低，包括天冬氨酸、谷氨酸、脱氢抗坏血酸、氨基丙二酸、甘氨酸、β - 丙氨酸和乙醇胺；而相对于健康对照大鼠，有11种代谢物在CUMS组中增加，即赤藓糖酸、果糖、β - 生育酚、5'- 单磷酸腺苷、5 - 羟色胺、乙醇酸、α - 生育酚、十四烷酸、肌酐、4,5 - 二甲基 - 2,6 - 二羟基嘧啶和肌醇。这些分子变化与神经递质代谢、能量代谢和氧化应激代谢的紊乱密切相关。这些差异代谢物的生化功能分析表明，神经递质、能量和氧化代谢的改变可能在MDD的发病机制中起作用，这可能对MDD的临床诊断有重要帮助。
