BACKGROUND Our understanding of the molecular mechanisms of depression remains largely unclear. Previous studies have shown that the prefrontal cortex (PFC) is among most important brain regions that exhibits metabolic changes in depression. A comprehensive analysis based on candidate metabolites in the PFC of animal models of depression will provide valuable information for understanding the pathogenic mechanism underlying depression. METHODS Candidate metabolites that are potentially involved in the metabolic changes of the PFC in animal models of depression were retrieved from the Metabolite Network of Depression Database. The significantly altered metabolic pathways were revealed by canonical pathway analysis, and the relationships among altered pathways were explored by pathway crosstalk analysis. Additionally, drug-associated pathways were investigated using drug-associated metabolite set enrichment analysis. The interrelationships among metabolites, proteins, and other molecules were analyzed by molecular network analysis. RESULTS Among 88 candidate metabolites, 87 altered canonical pathways were identified, and the top five ranked pathways were tRNA charging, the endocannabinoid neuronal synapse pathway, (S)-reticuline biosynthesis II, catecholamine biosynthesis, and GABA receptor signaling. Pathway crosstalk analysis revealed that these altered pathways were grouped into three interlinked modules involved in amino acid metabolism, nervous system signaling/neurotransmitters, and nucleotide metabolism. In the drug-associated metabolite set enrichment analysis, the main enriched drug pathways were opioid-related and antibiotic-related action pathways. Furthermore, the most significantly altered molecular network was involved in amino acid metabolism, molecular transport, and small molecule biochemistry. CONCLUSIONS This study provides important clues for the metabolic characteristics of the PFC in depression.

中文翻译：

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抑郁症动物模型的代谢组学分析。

背景我们对抑郁症的分子机制的理解在很大程度上仍不清楚。先前的研究表明，前额叶皮层 (PFC) 是抑郁症中表现出代谢变化的最重要的大脑区域之一。基于抑郁症动物模型 PFC 中候选代谢物的综合分析将为理解抑郁症的发病机制提供有价值的信息。方法 从抑郁症代谢物网络数据库中检索可能参与抑郁症动物模型中 PFC 代谢变化的候选代谢物。通过经典途径分析揭示显着改变的代谢途径，并通过途径串扰分析探索改变途径之间的关系。此外，使用药物相关代谢物集富集分析研究药物相关途径。通过分子网络分析来分析代谢物、蛋白质和其他分子之间的相互关系。结果 在 88 个候选代谢物中，确定了 87 个改变的经典途径，排名前五的途径是 tRNA 充电、内源性大麻素神经元突触途径、(S)-网状番荔枝碱生物合成 II、儿茶酚胺生物合成和 GABA 受体信号传导。通路串扰分析显示，这些改变的通路分为三个相互关联的模块，涉及氨基酸代谢、神经系统信号/神经递质和核苷酸代谢。在药物相关代谢物集富集分析中，主要富集的药物通路是阿片类药物相关和抗生素相关作用通路。此外，最显着改变的分子网络涉及氨基酸代谢、分子转运和小分子生物化学。结论 本研究为抑郁症患者 PFC 的代谢特征提供了重要线索。