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Objective Although depressive disorder is a serious neuropsychiatric illness,its pathogenesis remains unclear.Current evidence suggests that the abnormal transmission of hippocampal synapses is one of the most important pathogenesis of depressive disorder.In order to provide clues for studies on the synaptic pathogenesis of depression,the differential proteins of hippocampal synapses in a rat depression model was analyzed by two-dimensional gel electrophoresis.Methods After establishment of rat depression model via CMS experimental mode,rat hippocampal synapses from the CMS and contol groups were prepared by discontinuous sucrose density gradient centrifugation.Subsequently,the differential proteomics analysis were performed by conventional two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS).Results By 2DE combined with mass spectrometry analysis (2DE-MS),16 differentially expressed proteins were obtained,of which 12 were up-regulated and 4 were down-regulated in the chronic mild stressed group as compared with the control group.Conclusions By the comparative proteomics analysis and subsequent protein function prediction,we revealed some differentially expressed proteins related with energy metabolism obstacles in depression-model rats,which may participate in an important mechanism that underlies the abnormal transmission of hippocampal synapses found in the chronic mild stressed rat.thereby providing valuable clues for studies on the pathogenesis of depression.