Quercetin exerts antidepressant and cardioprotective effects in estrogen receptor α-deficient female mice via BDNF-AKT/ERK1/2 signaling.

• Estrogen receptor α deficiency produced a depression-like effect in the tail suspension test and forced swimming test of female mice. • Estrogen receptor α deficiency affected cardiac function by aggravating cardiomyocyte disorders of female mice. • Estrogen receptor α deficiency simultaneously influenced BDNF-AKT/ERK1/2 signaling in the hippocampus and heart of female mice. • Quercetin alleviated ERα-/--induced depression-like responses and cardiac dysfunction through BDNF-TrkB-AKT and ERK1/2 signaling. Brain-derived neurotrophic factor (BDNF) is the potential link between depression and cardiovascular disease and estrogen receptor α (ERα), an estrogen-mediated major regulator, plays an important role in protecting against depression and cardiovascular disease. However, the relationship between BDNF and ERα remains obscure. Herein, quercetin (QUE), a kind of plant flavonoids and existed in many vegetables and fruits, was found to simultaneously reverse ERα−/−-induced depression-like and cardiac dysfunction by reducing immobility time in the tail suspension test (TST) and forced swimming test (FST), and decreasing systolic blood pressure and activating the apoptosis-related proteins, BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), and extracellular regulatory protein kinase (ERK1/2) in the hippocampal and cardiac tissues of female mice. These findings suggested that ERα might be involved in the regulation of BDNF activity, thereby regulating depression-like and cardiovascular responses in female mice, and QUE exerted significant antidepressant and cardioprotective effects, at least in part, through BDNF-TrkB-AKT/ERK1/2 to effectively inhibit ERα−/−-induced hippocampal and cardiac dysfunction. [ABSTRACT FROM AUTHOR]