iTRAQ-Based Proteomics Suggests Ephb6 as a Potential Regulator of the ERK Pathway in the Prefrontal Cortex of Chronic Social Defeat Stress Model Mice

Abstract

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 proteomic-based strategy is used to compare the prefrontal cortex (PFC) in chronic social defeat stress (CSDS) model mice with a control group. Based on pooled samples, differential proteins are identified in the PFC proteome using iTRAQ coupled with LC-MS/MS.

Results: Ingenuity Pathway Analysis (IPA) is 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 are 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.

Keywords: EphB6; chronic social defeat stress; iTRAQ; major depressive disorder; prefrontal cortex.