Targeted Metabolomic Pathway Analysis and Validation Revealed Glutamatergic Disorder in the Prefrontal Cortex among the Chronic Social Defeat Stress Mice Model of Depression.
Targeted Metabolomic Pathway Analysis and Validation Revealed Glutamatergic Disorder in the Prefrontal Cortex among the Chronic Social Defeat Stress Mice Model of Depression.
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DOI：
10.1021/acs.jproteome.6b00577
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发表时间：
2016-09
影响因子：
4.4
通讯作者：
Wei Wang;Hua Guo;Shuxiao Zhang;Juan Li;K. Cheng;S. Bai;De-yu Yang;Haiyang Wang;Zihong Liang-Zih
中科院分区：
文献类型：
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作者：
Wei Wang;Hua Guo;Shuxiao Zhang;Juan Li;K. Cheng;S. Bai;De-yu Yang;Haiyang Wang;Zihong Liang-Zih
重度抑郁症（MDD）是一种严重的精神疾病，严重影响了数百万人的生活质量。慢性应激逐渐被认为是MDD的主要发病危险因素。尽管机制研究取得了显著进展，但MDD的发病机制仍不清楚。因此，我们进行了液相色谱-串联质谱法（LC-MS/MS）检测的25个主要代谢产物的前额叶皮层（PFC）在慢性社会失败应激（CSDS）的多巴胺，γ-氨基丁酸能和儿茶酚胺能途径。抑郁小鼠表现出GABA能途径中谷氨酸的显著减少和儿茶酚胺能途径中左旋多巴和香草基扁桃酸的增加。实时定量聚合酶链反应（RT-qPCR）和蛋白质印迹分析的数据揭示了一个改变的水平的多巴胺能电路。代谢组学和分子生物学数据显示，小鼠中的代谢能障碍揭示了抑郁样和应激弹性表型的机制。
Major depressive disorder (MDD) is a severe psychiatric disease that has critically affected life quality for millions of people. Chronic stress is gradually recognized as a primary pathogenesis risk factor of MDD. Despite the remarkable progress in mechanism research, the pathogenesis mechanism of MDD is still not well understood. Therefore, we conducted a liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection of 25 major metabolites of tryptophanic, GABAergic, and catecholaminergic pathways in the prefontal cortex (PFC) of mice in chronic social defeat stress (CSDS). The depressed mice exhibit significant reduction of glutamate in the GABAergic pathway and an increase of L-DOPA and vanillylmandelic acid in catecholaminergic pathways. The data of real-time-quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis revealed an altered level of glutamatergic circuitry. The metabolomic and molecular data reveal that the glutamatergic disorder in mice shed lights to reveal a mechanism on depression-like and stress resilient phenotype.