Integrated metabolomics and lipidomics profiling of hippocampus reveal metabolite biomarkers in a rat model of chronic unpredictable mild stress-induced depression
Integrated metabolomics and lipidomics profiling of hippocampus reveal metabolite biomarkers in a rat model of chronic unpredictable mild stress-induced depression
复制标题
海马体的综合代谢组学和脂质组学分析揭示了慢性不可预测的轻度应激性抑郁症大鼠模型中的代谢生物标志物
DOI：
10.21037/atm.2019.11.21
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发表时间：
2019-12-01
影响因子：
--
通讯作者：
Jiang, Pei
中科院分区：
文献类型：
--
作者：
Geng, Chunmei;Qiao, Yi;Jiang, Pei
背景：长期承受压力会引发抑郁症，威胁人类健康。因此，迫切需要彻底了解慢性不可预测的轻度应激（CUMS）引起的抑郁症的潜在病理生理机制。基于超高效液相色谱-质谱（UPLC-MS）的脂质组学和代谢组学方法已被用于发现代谢物生物标志物，以开发新的诊断和治疗手段。因此，我们的研究旨在进行综合代谢组学和脂质组学，以鉴定 CUMS 诱导的抑郁症大鼠模型海马中的代谢物和脂质生物标志物。 方法：将 12 只 8 周大的雄性 Sprague-Dawley 大鼠（体重 210 +/- 30 g）随机分配到以下两组之一（n = 6）：对照组或 CUMS。使用已建立的基于 UPLC-MS 的脂质组学和代谢组学方法来测定大鼠海马中的代谢物和脂质。利用SICMA-P和GraphPad软件发现两组大鼠海马区潜在代谢物和脂质生物标志物。结果：共鉴定出35种潜在代谢物和171种脂质，发现主要与氨基酸和脂质代谢相关。这些代谢物参与不同的代谢途径并相互联系，可能参与抑郁症的发生和发展。结论：我们的研究结果强调了与对照组相比，CUMS海马中代谢物、脂质和代谢途径的变化，为大鼠海马代谢提供了新的见解，并揭示了新的脂质相关靶点。
Background: Prolonged exposure to stress triggers depression, threatening human health. Thus, to thoroughly understand the underlying pathophysiologic mechanism of chronic unpredictable mild stress (CUMS)-induced depression is urgently needed. Ultra-high-performance liquid chromatography-mass spectroscopy (UPLC-MS)-based lipidomic and metabolomic approaches has been used for discovering metabolite biomarkers to develop new diagnostic and therapeutic means. Thus, our study aimed to conduct integrated metabolomics and lipidomics to identify metabolites and lipids biomarkers in the hippocampus in rat models of CUMS-induced depression.Methods: Twelve eight-week-old male Sprague-Dawley rats (weight 210 +/- 30 g) were randomly distributed to one of the following two groups (n=6): control or CUMS. Established UPLC-MS-based lipidomic and metabolomic approaches were used to determine the metabolites and lipids in the hippocampus of rats. SICMA-P and GraphPad software were performed to discover potential metabolites and lipids biomarkers in the hippocampus of rats between the two groups.Results: A total of 35 potential metabolites and 171 lipids were identified and found to be mainly related to amino acid and lipid metabolism. These metabolites were involved in different metabolic pathways and connected to each other, which might participate in the occurrence and development of depression.Conclusions: Our findings underlined the metabolites, lipids and metabolic pathways that were changed in the hippocampus in CUMS compared to the controls, providing novel insights in the metabolism in the hippocampus of rats and revealing the new lipid-related targets.