title: Hypothalamic Proteomic Analysis Reveals Dysregulation of Glutamate Balance and Energy Metabolism in a Mouse Model of Chronic Mild Stress-Induced Depression.
abstract: Hypothalamus-pituitary-adrenal (HPA) axis hyperactivity is observed in many patients suffering from depression. However, the mechanism underlying the dysfunction of the HPA axis is not well understood. Moreover, dysfunction of the hypothalamus, the key brain region of the HPA axis, has not been well-explored. The aim of our study was to examine possible alterations in hypothalamus protein expression in a model of depression using proteomic analysis. In order to achieve this aim, mice were exposed to chronic unpredictable mild stress (CUMS), as the paradigm results in hyperactivity of the HPA axis. Differential protein expression between the hypothalamic proteomes of CUMS and control mice was then assessed through two-dimensional electrophoresis followed by matrix-assisted laser desorption ionization-time of flight-tandem mass spectrometry. Thirty-seven proteins with a threshold of a 1.5-fold change and a p value ≤0.05 were identified as being differentially expressed between CUMS and control mice, and were quantified for bioinformatics analysis. Glycometabolism, citrate cycle (TCA cycle) and oxidation respiratory chain were found to have changed significantly. Glial fibrillary acidic protein and glutamine synthetase were further validated by Western Blot. Our results demonstrated that CUMS mice exhibited a dramatic protein change both in glutamate metabolism and energy mobilization, which may shed some light on the role of the hypothalamus in the pathology of stress-induced depression.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Rao
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Ziye
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Tang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: You
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China. xiepeng@cqmu.edu.cn.|Chongqing Key Laboratory of Neurobiology, Chongqing, China. xiepeng@cqmu.edu.cn.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. xiepeng@cqmu.edu.cn.|Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing, 400016, China. xiepeng@cqmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D003866:Depressive Disorder / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D013312:Stress, Physiological
chemical_list: D018698:Glutamic Acid; D003345:Corticosterone
keywords: Energy metabolism; Glutamate balance; Hypothalamus; Major depressive disorder; Proteomic