Hippocampal synaptic dysregulation of exo/endocytosis-associated proteins induced in a chronic mild-stressed rat model

Abstract

Although major depressive disorder (MDD) is a serious neuropsychiatric illness, it’s pathogenesis remains unclear. Current evidence suggests that the abnormal transmission and plasticity of hippocampal synapses play an important role in the pathogenesis of MDD. In this study, a two-dimensional gel-based proteomic approach to profile alterations of synaptosome protein expression was applied in the hippocampus of rats subjected to chronic mild stress.Through mass spectrometry and database searching, 19 differentially expressed proteins were identified, of which 5 were up-regulated and 14 were down-regulated in the chronic mild-stressed group as compared with the control group. Subsequently, several proteins of interest were further validated by Western blotting. A detailed analysis of protein functions and disease relevance revealed that synaptic exo/endocytosis-associated proteins were dysregulated in the chronic mild-stressed rats.The present study is the first reported synaptoproteomic analysis of the chronic mild-stressed rat hippocampus. The synaptic exo/endocytosis-associated proteins may participate in a central mechanism that underlies the abnormal transmission and plasticity of hippocampal synapses found in the chronic mild-stressed rats, and provides guidance to advance our understanding of the pathogenesis of MDD.