Quantitative proteomic study of the plasma reveals acute phase response and LXR/RXR and FXR/RXR activation in the chronic unpredictable mild stress mouse model of depression.

Abstract

Major depressive disorder is a severe neuropsychiatric disease that negatively impacts the quality of life of a large portion of the population. However, the molecular mechanisms underlying depression are still unclear. The pathogenesis of depression involves several brain regions. However, most previous studies have focused only on one specific brain region. Plasma and brain tissues exchange numerous components through the blood-brain barrier. Therefore, in the present study, plasma samples from control (CON) mice and mice subjected to chronic unpredictable mild stress (CUMS) were used to investigate the molecular pathogenesis of depression, and the association between the peripheral circulation and the central nervous system. A total of 47 significant differentially expressed proteins were identified between the CUMS and CON group by an isobaric tag for relative and absolute quantitation (iTRAQ) coupled with tandem mass spectrometry approach. These 47 differentially expressed proteins were analyzed with ingenuity pathway analysis (IPA) software. This revealed that the acute phase response, LXR/RXR and FXR/RXR activation, the complement system and the intrinsic prothrombin activation pathway were significantly changed. Four of the significant differentially expressed proteins (lipopolysaccharide binding protein, fibrinogen β chain, α-1 antitrypsin, and complement factor H) were validated by western blotting. the present findings provide a novel insight into the molecular pathogenesis of depression.