Estrogen may protect against heart failure-related depression by preventing the production of inflammation-causing chemicals in the brain. The study is published ahead of print in the American Journal of Physiology - Heart and Circulatory Physiology.
Research suggests that people with heart failure--including those who survive heart attacks--are two to three times more likely to suffer from depression than the general population. The reason for heart failure-related depression is thought to be increased inflammation in the brain. Previous studies have also found that post-menopausal women with heart disease have a greater risk of depression than younger women and men of all ages.
Researchers from the University of Ottawa Heart Institute and Brain and Mind Institute in Canada studied a rat model of heart failure after heart attack. Adult female rats without ovaries--mimicking menopause--were compared to adult males and adult females with ovaries. Half of the "menopausal" rats received estrogen supplements while the other half did not. Sex-matched rats without heart failure served as controls. The animals were given several standardized tests to assess depression-like behavior, learning, memory and the ability to experience pleasure. The researchers also took blood samples to measure inflammation levels in the brain (neuroinflammation).
The male rats, but not the female rats, with heart failure showed signs of depression and brain inflammation compared to their controls. In contrast, the menopausal females displayed higher rates of depression-like behavior than all of the males studied. However, the group receiving estrogen showed no depression--their levels were on par with the control females with ovaries--and no increase in inflammation in brain areas involved in mood and pleasure.
"Our findings demonstrate that sex and estrogens influence neuroinflammation and depression-like behavior in rats with [heart failure] post [heart attack]," the researchers wrote. "Understanding the mechanisms contributing to these sex-specific and estrogen-dependent responses may contribute to new therapies that may be sex-specific."
Patients with heart failure (HF) have a high prevalence of depression associated with a worse prognosis, particularly in older women. This study evaluated whether sex and estrogens affect depression-like behavior and associated neuroinflammation induced by myocardial infarction (MI) in rats. MI was induced by occlusion of the left anterior descending artery in young adult male and female Wistar rats or in ovariectomized (OVX) female rats without and with estrogen (17β-estradiol, E2) replacement. MI groups showed a comparable degree of cardiac dysfunction. Eight weeks post MI, male rats with HF exhibited depression-like behaviors including anhedonia and higher immobility in the sucrose preference and forced swim tests that was not observed in female rats with HF. In the cued fear conditioning test, the male, but not female rats with HF froze more than sham rats. After OVX, female sham rats developed mild depression-like behaviors that were pronounced in OVX female rats post MI and were largely prevented by E2 replacement. Cytokine levels in the plasma and paraventricular nucleus increased in both sexes with HF, but only male rats with HF showed an increase in cytokine levels in the prefrontal cortex. OVX alone did not affect cytokine levels, but OVX-MI caused significant increases in the prefrontal cortex which were shifted to an anti-inflammatory pattern by E2 replacement. These results suggest that estrogens prevent depression-like behavior induced by HF post MI in young adult female rats by inhibiting pro-inflammatory cytokines production and actions in the prefrontal cortex.
Najjar F, Ahmad M, Lagace D, Leenen FHH. Sex Differences in Depression-Like Behavior and Neuroinflammation in Rats Post MI: Role of Estrogens. Am J Physiol Heart Circ Physiol. 2018 Jul 27. doi: 10.1152/ajpheart.00615.2017. [Epub ahead of print]