G-1 exhibit antidepressant effect, increase of hippocampal ERs expression and improve hippocampal redox status in aged female rats

• Published in: Behavioural brain research 2019-02, Vol.359, p.845-852
• Main Authors: Wang, Jing, Yu, Rui, Han, Qiu-Qin, Huang, Hui-Jie, Wang, Ya-Lin, Li, Hao-Yuan, Wang, Hui-Mei, Chen, Xiao-Rong, Ma, Shu-Lan, Yu, Jin
• Format: Article
• Language: English
• Subjects: Aging - drug effects; Animals; Cyclopentanes - pharmacology; Depression; Disease Models, Animal; Estrogen receptors; Estrogens - blood; Exploratory Behavior - drug effects; Female; Gene Expression Regulation - drug effects; GPER; Hippocampus - drug effects; Hippocampus - ultrastructure; Maze Learning - drug effects; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondrial protection; Mood Disorders - drug therapy; Oestradiol; Ovariectomy; Oxidation-Reduction - drug effects; Oxidative Stress - drug effects; Quinolines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Estrogen - metabolism; Superoxide Dismutase - metabolism; Swimming - psychology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2018.07.017

•GPER agonist G-1 exhibit antidepressant- and anxiolytic-like effects in aged female rats.•G1 rescues the ERs level in hippocampus in aged female rats.•G1 alleviates hippocampal redox status in aged female rats.•G1 upregulate UCP2 and Bcl2 protein levels in hippocampus in aged female rats. 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.