Depression Model-based Metabolomics Study To Explore The Impact Of Depression On The Cardiovascular System

Depression is frequently comorbid with cardiovascular diseases (CVDs), but the full understanding of mechanisms is still on its way. Chronic unpredictable mild stress (CUMS) model is a commonly used model to mimic clinical depression, here we present a GC/MS-based metabolic profiling approach to investigate myocardial metabolic changes of CUMS SD rats. Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) were utilized to reveal differences between the model and control group. This study found that molecules proved cardioprotective involving glutamine (P=0.019) and inosine (P=0.013), fatty acid (9,12-Octadecadienoic acid, P=0.002; Hexadecanoic acid, P=0.006; Octadecanoic acid, P=0.030) which serve as the major energy source of heart and collagen molecule precursor proline (P=0.036) had down-regulated in CUMS model group.The normal lipids, aldehyde dehydrogenase2(ALDH2) and adiponectin levels are critical for cardiovascular function. This study investigated their changes in CUMS model of SD rats. Furthermore, the effects of sertraline treatment were also discussed. Rats exposed to CUMS showed a significant decrease of sucrose preference and hippocampus BDNF, which indicated successful model building. CUMS decreased the expression of serum adiponectin, high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and free fatty acid (FFA). The sertraline treatment restored the changes of serum adiponectin and HDL-C significantly. In myocardium, the protein level of adiponectin also decreased significantly in CUMS group, its receptors AdipoR1and AdipoR2were regulated in a different trend (AdipoR1decreased and AdipoR2increased); ALDH2decreased significantly here. In hippocampus, adiponectin mRNA was found, which indicated the possibility of adiponectin expression here; The adiponectin level decreased, its receptors AdipoR1and AdipoR2were compensatory up-regulated significantly; ALDH2level increased and its function in depression needs further study. These alternations in CUMS group were partly restored by sertraline treatment. Taken together, this study provides the evidence that stress down-regulated the cardio-protective agents of HDL-C, adiponectin and ALDH2, which responds for the elevated CVDs risk in depression. The sertraline treatment in depression has potential benefit on cardiovascular system.The exercise metabolomics study on depression model hasn’t been reported. Experiment was carried out using UPLC-MS technology, combined with high-dimensional statistical analysis of PLS-DA. How forced swimming influenced the metabolic profiling of health and depression model rats was studied. The results showed that70min/d forced swimming caused normal rats reducing the amount of sugar preferences and the hippocampal BDNF levels; On the other hand, the forced swimming partially up-regulated the amount of sugar preferences and BDNF levels compared with model group. Four groups were clearly separated in PLS-DA score plot. The first principal component of this model reflects the forced swimming and CUMS regulated the metabolites to the same trend, the second component reflects their counter effect. S-plot for screening biomarkers and glycolipids biochemical tests were carried out. The forced swimming restored the decreased adiponectin and increased glucose level of model rats. HDL-C, total cholesterol, lysophosphatidylcholine, valine, creatinine, tryptophan, phenylalanine and so on were significantly different between the control group and model group. This paper contains26figures,7tables and184references.