Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Behav Brain Res. 2021 Aug 27;412:113407. doi: 10.1016/j.bbr.2021.113407. Epub 2021 Jun 8.
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.
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.
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.
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.
抑郁症是全球范围内导致残疾的主要原因。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，其潜在机制仍知之甚少。
我们建立了慢性社会挫败应激（CSDS）大鼠模型，并进行了一系列行为测试来观察行为变化。然后采用基于液相色谱-质谱（LC-MS）的代谢组学和基于等重标记相对和绝对定量（iTRAQ）的蛋白质组学技术分别检测杏仁核中的代谢组和蛋白质组。采用通路分析（IPA）和其他生物信息学分析方法对差异表达的代谢物和蛋白质进行分析。
CSDS 大鼠在蔗糖偏好试验中的蔗糖偏好指数显著降低，在强迫游泳试验中的不动时间显著延长。在多组学分析中，鉴定出 37 个差异表达的代谢物和 123 个差异表达的蛋白质。IPA 对差异表达的代谢物和蛋白质进行综合分析，结果表明分子变化主要与突触可塑性、磷脂酶 C 信号转导和谷氨酰胺降解 I 有关。我们比较了杏仁核、海马体和前额叶皮质中的代谢物，发现这三个脑区有两种共同的代谢物：花生四烯酸和 N-乙酰-L-天冬氨酸。
本研究揭示了 CSDS 大鼠模型中存在抑郁样行为和杏仁核的分子变化，这可能为抑郁症的发病机制提供了进一步的认识，并有助于确定潜在的抗抑郁药物靶点。
