Proteomic and metabolomic characterization of amygdala in chronic social defeat stress rats
Proteomic and metabolomic characterization of amygdala in chronic social defeat stress rats
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慢性社交失败应激大鼠杏仁核的蛋白质组学和代谢组学特征
DOI：
10.1016/j.bbr.2021.113407
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发表时间：
2021-06-12
影响因子：
2.7
通讯作者：
Xie, Peng
中科院分区：
文献类型：
--
作者：
Fan, Li;Yang, Lining;Xie, Peng
背景：抑郁症是全球残疾的主要原因。越来越多的证据表明抑郁症与杏仁核的病理生理学有关，然而，其潜在机制仍然知之甚少。方法：建立慢性社会失败应激（CSDS）大鼠模型，通过一系列行为学测试观察其行为学变化。然后分别采用基于液相色谱-质谱（LC-MS）的代谢组学和基于同量异位素相对和绝对定量标签（iTRAQ）的蛋白质组学方法检测杏仁核中的代谢组和蛋白质组。利用免疫途径分析（IPA）和其他生物信息学分析来分析差异表达的代谢产物和蛋白质。结果如下：与对照组相比，CSDS组大鼠在蔗糖偏好实验中蔗糖偏好指数显著降低，在强迫游泳实验中不动时间显著延长。在多组学分析中，确定了37个显著差异表达的代谢产物和123个显著蛋白质。通过IPA对差异表达的代谢产物和蛋白质的综合分析显示，分子变化主要与突触可塑性、磷脂酶C信号传导和谷氨酰胺降解I相关。我们比较了杏仁核、海马和前额叶皮层的代谢产物，发现这三个脑区有两个共同的代谢产物：花生四烯酸和N-乙酰-L-天冬氨酸。结论：我们的研究揭示了CSDS大鼠模型中抑郁样行为和杏仁核分子变化的存在，这可能为进一步了解抑郁症的发病机制提供帮助，并有助于确定抗抑郁药的潜在靶点。
Background: Depression is a leading cause of disability worldwide. There is increasing evidence showing that depression is associated with the pathophysiology in amygdala; however, the underlying mechanism remains poorly understood. Method: We established a rat model of chronic social defeat stress (CSDS) and conducted a series of behavior tests to observe behavioral changes. Then liquid chromatography mass spectrometry (LC-MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed to detect metabolomes and proteomes in the amygdala, respectively. Ingenuity pathway analysis (IPA) and other bioinformatic analyses were used to analyze differentially expressed metabolites and proteins. Results: The significantly lower sucrose preference index in the sucrose preference test and longer immobile time in the forced swim test were observed in the CSDS rats compared with control rats. In the multi-omics analysis, thirty-seven significantly differentially expressed metabolites and 123 significant proteins were identified. Integrated analysis of differentially expressed metabolites and proteins by IPA revealed molecular changes mainly associated with synaptic plasticity, phospholipase c signaling, and glutamine degradation I. We compared the metabolites in the amygdala with those in the hippocampus and prefrontal cortex from our previous studies and found two common metabolites: arachidonic acid and N-acetyl-L-aspartic acid among these three brain regions. Conclusion: Our study revealed the presence of depressive-like behaviors and molecular changes of amygdala in the CSDS rat model, which may provide further insights into the pathogenesis of depression, and help to identify potential targets for antidepressants.