Targeted Metabolomic Pathway Analysis and Validation Revealed Glutamatergic Disorder in the Prefrontal Cortex among the Chronic Social Defeat Stress Mice Model of Depression.
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.
Department of Neurology, Yongchuan Hospital of Chongqing Medical University , Chongqing 402460, China.|Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.
Wei
W
Wang
Department of Neurology, Yongchuan Hospital of Chongqing Medical University , Chongqing 402460, China.|Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.
Hua
H
Guo
Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.
Shu-Xiao
SX
Zhang
Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.|Department of Neurology, the First Affiliated Hospital of Chongqing Medical University , Chongqing 400016, China.
Juan
J
Li
Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.|Department of Neurology, the First Affiliated Hospital of Chongqing Medical University , Chongqing 400016, China.
Ke
K
Cheng
Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.
Shun-Jie
SJ
Bai
Department of Neurology, Yongchuan Hospital of Chongqing Medical University , Chongqing 402460, China.
De-Yu
DY
Yang
Department of Neurology, Yongchuan Hospital of Chongqing Medical University , Chongqing 402460, China.|Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.
Hai-Yang
HY
Wang
Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.|Department of Neurology, the First Affiliated Hospital of Chongqing Medical University , Chongqing 400016, China.
Zi-Hong
ZH
Liang
Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.
Li
L
Liao
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University , Chongqing 400016, China.
Lin
L
Sun
Department of Neurology, Yongchuan Hospital of Chongqing Medical University , Chongqing 402460, China.|Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University , Chongqing 400016, China.|Chongqing Key Laboratory of Neurobiology , Chongqing 400016, China.|Department of Neurology, the First Affiliated Hospital of Chongqing Medical University , Chongqing 400016, China.
Peng
P
Xie
D000818:Animals; D015153:Blotting, Western; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D017397:Prefrontal Cortex / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013315:Stress, Psychological / Q000378:metabolism
D018698:Glutamic Acid
CSDS; LC-MS/MS; depression; glutamate; metabolomics