title: Dynamic proteomic analysis of protein expression profiles in whole brain of Balb/C mice subjected to unpredictable chronic mild stress: implications for depressive disorders and future therapies.
abstract: The etiology and pathophysiology of depression remain unknown. Previous works were mostly performed on single observation time-point which might be insufficiently to reveal the molecular events changed during the disease development. Adult BALB/c mice were exposed to unpredictable chronic mild stress (UCMS) for different periods and differential 2D gel electrophoresis (DIGE) approach was employed to the brain tissue to explore the molecular disease signatures. Sustained elevation of corticosterone level was observed, suggesting the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis when the mice were subjected to the stressful situation. The behavioral results indicated the depressive alterations of the mice exposing to UCMS. The altered proteins identified by proteomics showed that abnormal energy mobilization under stress condition was accompanied by overproduction of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. Cytoskeleton protein and anti-oxidant enzymes were also changed by UCMS treatment. The results of biochemical and immunohistochemical assay confirmed the changes identified by DIGE analysis. These results indicated that the insufficiency of ATP synthesis, overwhelming ROS production and ER stress subsequently contributed to the cytoskeletal damage and inhibition to expression of some anti-oxidant proteins, which might ultimately bring functional neuron to apoptosis or death. Proteins whose expression is affected may provide tools for potential treatment strategies.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 5 Dongdansantiao, Beijing 100005, China.
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Wenyu
authors.initials: W
authors.lastname: Hao
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.forename: Tianyi
authors.initials: T
authors.lastname: Ying
authors.forename: Shangyi
authors.initials: S
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yilong
authors.initials: Y
authors.lastname: Dong
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.forename: Pingping
authors.initials: P
authors.lastname: Zuo
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D002908:Chronic Disease; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D004734:Energy Metabolism / Q000235:genetics; D005544:Forecasting; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000235:genetics; D040081:Protein Array Analysis / Q000379:methods; D040901:Proteomics / Q000379:methods*; D011897:Random Allocation; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*