Integrative Proteomics–Metabolomics Strategy for Pathological Mechanism of Vascular Depression Mouse Model

Vascular depression (VD), a subtype of depression, is caused by vascular diseases or cerebrovascular risk factors. Recently, the proportion of VD patients has increased significantly, which severely affects their quality of life. However, the current pathogenesis of VD has not yet been fully understood, and the basic research is not adequate. In this study, on the basis of the combination of LC-MS-based proteomics and metabolomics, we aimed to establish a protein metabolism regulatory network in a murine VD model to elucidate a more comprehensive impact of VD on organisms. We detected 44 metabolites and 304 proteins with different levels in the hippocampus samples from VD mice using a combination of metabolomic and proteomics analyses with an isobaric tags for relative and absolute quantification (iTRAQ) method. We constructed a protein-to-metabolic regulatory network by correlating and integrating the differential metabolites and proteins using ingenuity pathway analysis. Then we quantitatively validated the levels of the bimolecules shown in the bioinformatics analysis using LC-MS/MS and Western blotting. Validation results suggested changes in the regulation of neuroplasticity, transport of neurotransmitters, neuronal cell proliferation and apoptosis, and disorders of amino acids, lipids and energy metabolism. These proteins and metabolites involved in these dis-regulated pathways will provide a more targeted and credible direction to study the mechanism of VD. Therefore, this paper presents an approach and strategy that was applied in integrative proteomics and metabolomics for research and screening potential targets and biomarkers of VD, which could be more precise and credible in a field lacking adequate basic research.