iTRAQ-based proteomics suggests Ephb6 as a potential regulator of the ERK pathway in the prefrontal cortex of chronic social defeat stress model miceiTRAQ-based proteomics reveals Ephb6 as a potential regulator of the ERK pathway in the prefrontal cortex of chronic social defeat stress model mice

Purpose: Major depressive disorder (MDD) is a worldwide concern and devastating psychiatric disease. The World Health Organization claims that MDD leads to at least 11.9% of the global burden of disease. However, the underlying pathophysiology mechanisms of MDD remain largely unknown. Experimental design: Herein, we used a proteomic-based strategy to compare the prefrontal cortex (PFC) in chronic social defeat stress (CSDS) model mice with a control group. Based on pooled samples, differential proteins were identified in the PFC proteome using iTRAQ coupled with LC-MS/MS. Results: Ingenuity Pathway Analysis (IPA) was then followed to predict relevant pathways, with the ephrin receptor signaling pathway selected for further research. Additionally, as the selected key proteins of the ephrin receptor signaling pathway, ephrin type-B receptor 6 (EphB6) and the ERK pathway were validated by western blotting. Conclusion and clinical relevant: Altogether, increased understanding of the ephrin receptor signaling pathway in MDD is provided, which implicates further investigation of PFC dysfunction induced by CSDS treatment.