Exercise Training After Isoproterenol in Middle-Aged Female Rats Reversed Effects on the Heart, Without Affecting the Brain

Abstract Introduction Females with cardiovascular disease may be more susceptible to concomitant mental problems, such as depression and cognitive decline. Exercise training has beneficial effects on the cardiovascular system as well as on mental functions. Aim of the present study was to study the effects of exercise training on heart, brain and behavior in the isoproterenol (ISO) model in middle-aged female rats. Methods Twelve months old female Wistar rats were submitted to ISO injections (70 mg/kg s.c., on two consecutive days) or received saline. One week later, rats were assigned to either exercise training (treadmill running) or control handling for five weeks. During the last 7 days, tests were performed regarding depressive-like behavior and cognitive function. Then, rats were sacrificed and heart and brains were dissected for (immuno)histochemistry.Results ISO-induced cardiac effects were eminent from cardiac fibrosis and declined cardiac function. Exercise training reversed cardiac damage and partly restored ISO-induced cardiac dysfunction. However, ISO treatment could not be associated with neuroinflammation, nor impaired hippocampal neurogenesis or neuronal function. Accordingly, no mental problems, such as cognitive decline or depressive-like behavior were observed. Actually, hippocampal microglia hyper-ramification and increased sucrose preference were observed after ISO. Exercise left neuroinflammation and behavior merely unaltered, and even reduced neuronal function. Conclusion Our data indicated that the substantial cardiac damage after ISO in middle aged female rats, and the subsequent beneficial effects of five weeks exercise training on the heart, were not reflected in changes in the brain nor in altered behavior.