Ghrelin attenuates depressive-like behavior, heart failure, and neuroinflammation in postmyocardial infarction rat model

Depression after myocardial infarction (MI) and chronic heart failure (CHF) is a common condition that is resistant to anti-depressive drugs. Ghrelin (a peptide hormone) shows dual protective effects on heart and brain. Whether ghrelin treatment attenuated depression after MI was investigated. Coronary artery occlusion was performed to induce MI and subsequent CHF in rats. Ghrelin (100 μg/kg in 0.5 ml of saline) or vehicle (0.5 ml of saline) was injected subcutaneously twice a day for 4 weeks. At week 5, all the animals underwent behavioral assessments including sucrose preference test (SPT), elevated plus maze test (EPM), and open field test (OFT). After cardiac function analysis, brain tissues were processed to determine inflammatory cytokines and microglial activations in hippocampus. Results showed that ghrelin substantially improved cardiac dysfunction, infarction size, and cardiac remodeling and modulated the release of inflammatory cytokines and the increase of Iba-1 positive microglia and glial fibrillary acidic protein-positive astrocytes in the CA1 area of hippocampus. Behavioral tests revealed that this treatment remarkably increased sucrose preference and mobile times and numbers. These findings provided evidence that peripheral ghrelin administration inhibits depression-like behavior and neuroinflammation and thus could be a new approach for the treatment of CHF-associated depression.