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
Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China; Experimental Teaching Center, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Behav Brain Res. 2019 Feb 1;359:845-852. doi: 10.1016/j.bbr.2018.07.017. Epub 2018 Jul 21.
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.
绝经后抑郁症已被证明与女性从绝经阶段过渡到绝经后阶段时卵巢激素分泌减少有关。尚不清楚的是哪种类型的雌激素受体在雌激素神经保护中起关键作用，这一过程可能通过增强脑线粒体功能和抑制线粒体相关凋亡来介导。为了更好地模拟绝经后的状况，我们对老年雌性大鼠进行了研究。去卵巢大鼠和16月龄雌性大鼠的血浆雌激素水平显著下降，同时焦虑和抑郁样行为增加。此外，去卵巢后雌性大鼠海马中ERα、ERβ、GPER、Bcl2和UCP2的表达显著降低。在我们的研究中，用GPER激动剂G-1治疗后，老年雌性大鼠的焦虑和抑郁样行为得到显著缓解。此外，G-1可以逆转海马中ERα、ERβ、GPER、Bcl2和UCP2表达的降低。线粒体JC-1染色表明，G-1治疗后线粒体膜电位增加。此外，发现G-1治疗后老年雌性大鼠的总抗氧化能力（TAC）和超氧化物歧化酶活性（SOD）升高。综上所述，雌激素受体，尤其是GPER，可能激活抗凋亡信号并加速线粒体功能。因此，GPER可能是雌激素缺乏相关情感障碍的潜在治疗靶点。
