Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain

Abstract

Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI).Methods and Results: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF), and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI.Conclusions: After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.

The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease

“…Animal studies show depressive symptoms weeks after experimental myocardial infarction (Frey et al, 2014;Grippo et al, 2003;Schoemaker and Smits, 1994) that can be blocked by the TNF-a blocker Etanercept (Grippo et al, 2003).…”

Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity

“…Echocardiography was performed and evaluated as previously described 18. Serial cardiac ultrasound analyses were performed on a VisualSonics Vevo 1100 imaging system (Fujifilm, Tokyo, Japan) with a 30MHz ultrasound probe under light anesthesia with isoflurane (1.5 vol%) and spontaneous respiration by a single researcher experienced in rodent echocardiography who was blinded to the treatment group.…”

Learned helplessness reveals a population at risk for depressive‐like behaviour after myocardial infarction in mice

“…4 Patients with HF and co-morbid depression show poorer clinical outcome, including elevated morbidity, rate of hospitalization, and mortality. 14 In behavioural research, tests of individual symptoms of depression, e.g. Psychotherapy and antidepressant medication have not shown beneficial impact on patient outcome so far.…”