A Neuroendocrine Mechanism of Co-Morbidity of Depression-Like Behavior and Myocardial Injury in Rats

Abstract

Depression is generally a recurrent psychiatric disorder. Evidence shows that depression and cardiovascular diseases are common comorbid conditions, but the specific pathological mechanisms remain unclear. The purpose of this study is to determine the effects of depression induced by chronic unpredictable mild stress (CUMS) on myocardial injury and to further elucidate the biological mechanism of depression. Rats were used as a model. The CUMS procedure lasted for a total of 8 weeks. After 4 weeks of CUMS, treated rats exhibited a reduced sucrose preference and changes in scores on an open field test, body weight and content of 5-HT in the brain as compared with the values of these variables in controls. These changes indicated depression-like changes in CUMS rats and demonstrated the feasibility of the depression model. In addition, pathological changes in the myocardium and increased cardiomyocyte apoptosis demonstrated that myocardial injury had occurred after 6 weeks of CUMS and had increased significantly by the end of 8 weeks of CUMS. Plasma serotonin (5-HT), norepinephrine (NE) and epinephrine (E), all depression-related neuroendocrine factors, were measured by HPLC-ECD techniques, and the content of plasma corticosterone (GC) was evaluated by an I125–cortisol radioactivity immunoassay in control and CUMS rats. The results indicated that 5-HT had decreased, whereas NE, E and GC had increased in CUMS rats, and these factors might be associated with depression-induced myocardial injury. The effects of 5-HT, NE and GC on the survival rate of cultured cardiomyocytes were determined using an orthogonal design. The results showed that 5-HT was a more important factor affecting cell survival than GC or NE. The results suggested that normal blood levels of 5-HT had a cytoprotective effect. The neuroendocrine disorders characterized by decreased 5-HT combined with increased GC and NE mediated the occurrence of depression-induced myocardial injury.

Quercetin Inhibits Left Ventricular Dysfunction Induced by Chronic Stress in Rats

“…Our data which points to an effective rat model of CUS that caused substantial LV damage are in agreement with previous studies on CUS animal models; where mild type of CUS in rats induced the proapoptotic Bax protein in the myocardium (Dang et al, 2016), caused myocardial injury and increased cardiomyocyte apoptosis in cultured cells (Xinxing et al, 2014). In addition, the beneficial effects of quercetin on Wistar rats that was recently reported (Barteková et al, 2015) to (i) protect the left ventricle ultrastructure from damages cause by the chemotherapy drug doxorubicin; (ii) inhibited doxorubicin-induced caspase-3 in left ventricle tissues; and (iii) reversed the down-regulation of SOD by doxorubicin in left ventricle tissues, are in agreement with our data shown in Figures 1 and 3 on the protection of the same species of rats' left ventricles by quercetin upon CUS induction.…”

Deletion of TRIM32 protects mice from anxiety‐ and depression‐like behaviors under mild stress

“…In the present study, we found under the unpredictable chronic mild stress that mice developed depression‐ and anxiety‐like behaviors, which were most obvious in week 4, and some of the behaviors such as FST gradually recovered by week 8. The dynamic changes in these behaviors are consistent with previous reports (Guan et al ., ; Xinxing et al ., ), suggesting there is an adaptive response of animals to continuous stimuli. Interestingly, the behavioral changes coincided with down‐regulation of TRIM32 protein specifically in hippocampus in a time‐dependent manner.…”

High-Resolution Magic-Angle Spinning-¹H-NMR Spectroscopy-Based Metabolic Profiling of Hippocampal Tissue in Rats with Depression-Like Symptoms

“…26) Owing to the imposition of stress over time, the sucrose preference decreased in the CS group and was significantly lower on day 22 compared to the control group (p<0.05) (Fig. 2b).…”