title: iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression.
abstract: Major depressive disorder (MDD) is a prevalent psychiatric mood illness and a major cause of disability and suicide worldwide. However, the underlying pathophysiology of MDD remains poorly understood due to its heterogenic nature. Extensive pre-clinical research suggests that many molecular alterations associated with MDD preferentially localize to the postsynaptic density (PSD). Here, we used a rodent chronic mild stress (CMS) model to generate susceptible and unsusceptible subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass spectrometry was performed to identify differentially expressed proteins in enriched PSD preparations from the hippocampi of different groups. More than 1500 proteins were identified and quantified, and 74 membrane proteins were differentially expressed. Of these membrane proteins, 51 (69%) were identified by SynaptomeDB search as having a predicted PSD localization. The unbiased profiles identified several PSD candidate proteins that may be related to CMS vulnerability or insusceptibility, and these two CMS phenotypes displayed differences in the abundance of several types of proteins. A detailed protein functional analysis pointed to a role for PSD-associated proteins involved in signaling and regulatory functions. Within the PSD, the N-methyl-D-aspartate (NMDA) receptor subunit NR2A and its downstream targets contribute to CMS susceptibility. Further analysis of disease relevance indicated that the PSD contains a complex set of proteins of known relevance to mental illnesses including depression. In sum, these findings provide novel insights into the contribution of PSD-associated proteins to stress susceptibility and further advance our understanding of the role of hippocampal synaptic plasticity in MDD.
authors: Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors: X
authors: X
authors: Han
authors: Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors: W
authors: W
authors: Shao
authors: Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors: Z
authors: Z
authors: Liu
authors: Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors: S
authors: S
authors: Fan
authors: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors: J
authors: J
authors: Yu
authors: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors: J
authors: J
authors: Chen
authors: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors: R
authors: R
authors: Qiao
authors: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China. Electronic address: zhou_jian0615@163.com.
authors: J
authors: J
authors: Zhou
authors: Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China. Electronic address: xiepeng@cqmu.edu.cn.
authors: P
authors: P
authors: Xie
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D003863:Depression / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D046353:Immobility Response, Tonic; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications*; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D053719:Tandem Mass Spectrometry
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D013549:Sweetening Agents; C033652:postsynaptic density proteins; D013395:Sucrose
keywords: chronic mild stress; hippocampus; iTRAQ; major depressive disorder; postsynaptic density; proteomics