title: Quantitative Proteomic Analysis Reveals Molecular Adaptations in the Hippocampal Synaptic Active Zone of Chronic Mild Stress-Unsusceptible Rats.
abstract: BACKGROUND
  While stressful events are recognized as an important cause of major depressive disorder, some individuals exposed to life stressors maintain normal psychological functioning. The molecular mechanism(s) underlying this phenomenon remain unclear. Abnormal transmission and plasticity of hippocampal synapses have been implied to play a key role in the pathoetiology of major depressive disorder.
  
  
  METHODS
  A chronic mild stress protocol was applied to separate susceptible and unsusceptible rat subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation coupled with tandem mass spectrometry was performed to identify differential proteins in enriched hippocampal synaptic junction preparations.
  
  
  RESULTS
  A total of 4318 proteins were quantified, and 89 membrane proteins were present in differential amounts. Of these, SynaptomeDB identified 81 (91%) having a synapse-specific localization. The unbiased profiles identified several candidate proteins within the synaptic junction that may be associated with stress vulnerability or insusceptibility. Subsequent functional categorization revealed that protein systems particularly involved in membrane trafficking at the synaptic active zone exhibited a positive strain as potential molecular adaptations in the unsusceptible rats. Moreover, through STRING and immunoblotting analysis, membrane-associated GTP-bound Rab3a and Munc18-1 appear to coregulate syntaxin-1/SNAP25/VAMP2 assembly at the hippocampal presynaptic active zone of unsusceptible rats, facilitating SNARE-mediated membrane fusion and neurotransmitter release, and may be part of a stress-protection mechanism in actively maintaining an emotional homeostasis.
  
  
  CONCLUSIONS
  The present results support the concept that there is a range of potential protein adaptations in the hippocampal synaptic active zone of unsusceptible rats, revealing new investigative targets that may contribute to a better understanding of stress insusceptibility.
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie).
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie).
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie).
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie).
authors.forename: Xin
authors.initials: X
authors.lastname: Han
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie).
authors.forename: Songhua
authors.initials: S
authors.lastname: Fan
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie).
authors.forename: Weihua
authors.initials: W
authors.lastname: Shao
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie).
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie).
authors.forename: Rui
authors.initials: R
authors.lastname: Qiao
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Chongqing Key Laboratory of Neurobiology, Chongqing, China (Drs Zhou, Liu, Yu, Han, Fan, Shao, Chen, Qiao, and Xie); Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Liu, Han, Fan, Shao, and Xie). xiepeng@cqmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000220:Adaptation, Biological / Q000502:physiology*; D000818:Animals; D019295:Computational Biology; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051938:Munc18 Proteins / Q000378:metabolism; D040901:Proteomics; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050600:SNARE Proteins / Q000378:metabolism; D013315:Stress, Psychological / Q000473:pathology* / Q000503:physiopathology; D013550:Swimming; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D050988:Vesicle-Associated Membrane Protein 2; D020826:rab3A GTP-Binding Protein
keywords: chronic mild stress; hippocampus; major depressive disorder; proteomics; synapse