Abstract:
Major depressive disorder (MDD) is an independent risk factor for cardiovascular disease (CVD) and its complications; however, causal mechanisms remain unclear. In the present study, we investigate cardiac structural and functional alterations and associated changes in myocardial glycosaminoglycans (GAGs) disaccharide profile in mice that exhibit depression-like behavior. Mice were assigned to chronic mild stress group (CMS) and non-stress control group (CT). The CMS group was exposed to a series of mild, unpredictable stressors for 7 weeks. Mice in CMS group show a significant decrease in protein expression of hippocampal brain-derived neurotrophic factor (BDNF), and exhibit depression-like behavioral changes such as learned helplessness and decreased exploration behavior as compared to the control group. While cardiac function remained unchanged between the groups, echocardiography analysis showed slightly increased left ventricular wall thickness in the CMS group. Furthermore, CMS group shows an increase in cardiomyocyte cross-sectional area when compared to control mice. GAG disaccharide analysis of the left ventricles of the CMS and CT mice revealed an elevation in heparan (HS) and chondroitin sulfate (CS) content in the CMS hearts (35.3% and 17.9%, respectively vs. control group). Furthermore, we also observed that unsulfated or monosulfated disaccharides were the most abundant units; however, we did not find any significant difference in mole % or sulfation pattern of HS/CS disaccharides between the groups. The current investigation highlights a need for further research to explore the relationship between cardiac GAGs biology and myocardial remodeling as a causal mechanism that underlie cardiovascular complications in MDD patients. Learn more at DOI: 10.1152/ajpheart.00635.2020
