Chronic mild stress leads to aberrant glucose energy metabolism in depressed Macaca fascicularis models
Chronic mild stress leads to aberrant glucose energy metabolism in depressed Macaca fascicularis models
复制标题
慢性轻度应激导致抑郁猕猴模型葡萄糖能量代谢异常
DOI：
10.1016/j.psyneuen.2019.05.007
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发表时间：
2019-09-01
影响因子：
3.7
通讯作者：
Xie, Peng
中科院分区：
文献类型：
--
作者：
Qin, Yinhua;Jiang, XiaoFeng;Xie, Peng
背景资料：重性抑郁障碍（Major Depression Disorder，MDD）是一种病因和临床表现复杂、病理生理特征不明显的精神疾病。啮齿类抑郁症模型已被广泛用于模拟抑郁症的病态。然而，情绪障碍的研究也可以受益于使用模型在非人类灵长类动物，其中有广泛的遗传和社会相似性与human.Methods：探讨抑郁症的病理生理机制，我们建立了两个模型，自然发生的抑郁症食蟹猴（NOD）和社会加上视觉隔离引起的抑郁症食蟹猴（SVC），模仿慢性轻度或急性强烈的压力，分别。我们使用i-TRAQ（相对和绝对定量的同量异位素标签）为基础的定量蛋白质组学和鸟枪蛋白质组学，以确定差异表达的蛋白质在两个猴模型和人类MDD患者的脑脊液（CSF）。我们还使用大卫和独创性通路分析（IPA）进一步的生物信息学investigation.Results：在行为测试中，NOD猴取得了更高的分数，抑郁样和焦虑样的行为措施，并花费更多的时间在吞咽，体温调节，和运动动作比SVC猴。通过i-TRAQ共鉴定出902个蛋白质，在NOD-CON 1和SVC-CON 2组中各鉴定出40个差异表达蛋白质。大卫的应用揭示了NOD组能量代谢的失调，而SVC组的脂质代谢和炎症反应途径显著改变。IPA和Cytoscape的使用表明，氧物质代谢过程糖酵解I/糖异生I，伴随着微管蛋白β 3 III类（TUBB 3）、RAC-α丝氨酸/苏氨酸蛋白激酶（AKT 1）和甘油醛-3-磷酸脱氢酶（GAPDH）的下调，是NOD组中受影响最显著的途径。此外，在人类MDD患者中的152个差异表达蛋白也揭示了葡萄糖能量代谢的破坏。显着异常的能量代谢在不同的大脑区域和血浆和肝脏的慢性不可预测的轻度应激啮齿动物样品也观察到在以前的study.Conclusions：我们的研究结果揭示了第一次的整体CSF蛋白质谱的两个食蟹猴模型抑郁症。我们认为，慢性轻度应激可能会影响NOD食蟹猴和啮齿动物的葡萄糖能量代谢的破坏。这些发现促进了我们对MDD病理生理学的理解，并可能有助于确定新的治疗靶点。
Background: Major depressive disorder (MDD) is a pathophysiologically uncharacterized mental illness with complex etiology and clinical manifestations. Rodent depression-like models have been widely used to mimic the morbid state of depression. However, research on emotional disorders can also benefit from the use of models in non-human primates, which share a wide range of genetic and social similarities with humans.Methods: To investigate the pathophysiological mechanisms of depression, we established two models, naturally occurring depression cynomolgus (NOD) and social plus visual isolation-induced depression cynomolgus (SVC), imitating chronic mild or acute intense stress, respectively. We used i-TRAQ (isobaric tags for relative and absolute quantitation)-based quantitative proteomics and shotgun proteomics to identify differentially expressed proteins in cerebrospinal fluid (CSF) of the two monkey models and human MDD patients. We also used DAVID and ingenuity pathway analysis (IPA) for further bioinformatic investigation.Results: In behavioral tests, NOD monkeys achieved higher scores in depression-like and anxiety-like behavioral measures, and spent more time on ingesting, thermoregulatory, and locomotive actions than SVC monkeys. A total of 902 proteins were identified by i-TRAQ, and 40 differentially expressed proteins were identified in each of the NOD-CON1 and SVC-CON2 groups. Application of DAVID revealed dysregulation of energy metabolism in the NOD group, whereas lipid metabolism and inflammatory response pathways were significantly altered in the SVC group. Use of IPA and Cytoscape showed that the oxygen species metabolic process glycolysis I/gluconeogenesis I, accompanied by downregulation of tubulin beta 3 class III (TUBB3), RAC-alpha serine/threonine-protein kinase (AKT1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was the most significantly affected pathway in the NOD group. Furthermore, 152 differentially expressed proteins in human MDD patients also revealed disruption of glucose energy metabolism. Significantly aberrant energy metabolism in various brain regions and the plasma and liver of chronic unpredictable mild stress rodent samples were also observed in a previous study.Conclusions: Our results reveal for the first time the overall CSF protein profiles of two cynomolgus monkey models of depression. We propose that chronic mild stress may affect the disruption of glucose energy metabolism in NOD cynomolgus monkeys and rodents. These findings promote our understanding of the pathophysiology of MDD and may help to identify novel therapeutic targets.