1-(4-(6-bromobenzo(1-3)dioxol-5-yl)-3a-4-5-9b-tetrahydro-3h-cyclopenta(c)quinolin-8-yl)ethanone and Mood-Disorders

Postmenopausal depression has been shown to be related to the reduction of ovarian hormones produced as a woman transitions from a menopausal to a post-menopausal stage. What remains to be known is which type of estrogen receptor plays a key role in estrogen neuroprotection, a process that may be mediated by potentiating brain mitochondrial function and inhibiting mitochondria-associated apoptosis. In order to better imitate the condition of postmenopause, we conducted our research on aged female rats. Plasma estrogen levels declined significantly in ovariectomized rats and 16-month-old female rats, while anxiety and depression-like behavior increase. Moreover, ERα, ERβ, GPER, Bcl2 and UCP2 expression decreased significantly in hippocampus in female rats following ovariectomy. In our study, the anxiety and depression-like behavior in aged female rats were significantly relieved after the treatment of G-1, the GPER agonist. Furthermore, G-1 could reverse the reduction of ERα, ERβ, GPER, Bcl2 and UCP2 expression within the hippocampus. Mitochondrial JC-1 staining indicated that mitochondrial membrane potential increased after G-1 treatment. In addition, total antioxidant capacity (TAC) and superoxide dismutase activity (SOD) were found to be elevated in aged female rats following G-1 treatment. Taken together, estrogen receptors, especially GPER, may activate anti-apoptotic signaling and accelerate mitochondrial function. Therefore, GPER could be the potential therapeutic target for estrogen deficiency-related affective disorders.

Topics: Aging; Animals; Cyclopentanes; Disease Models, Animal; Estrogens; Exploratory Behavior; Female; Gene Expression Regulation; Hippocampus; Maze Learning; Membrane Potential, Mitochondrial; Mitochondria; Mood Disorders; Ovariectomy; Oxidation-Reduction; Oxidative Stress; Quinolines; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Superoxide Dismutase; Swimming