期刊
BEHAVIOURAL BRAIN RESEARCH
卷 359, 期 -, 页码 845-852出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2018.07.017
关键词
Oestradiol; Depression; Estrogen receptors; GPER; Mitochondrial protection
资金
- States Key Project of Research and Development Plan [2017YFB0403803]
- National Key Basic Research Program of China [2013CB531906]
- National Natural Science Fund of China [81671349, 81473437, 31371083, 81271500]
- Development Project of Shanghai Peak Disciplines-Integrated Chinese and Western Medicine
- Natural Science Fund of Shanghai [14ZR1405200]
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, ER alpha, ER beta, 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 ER alpha, ER beta, 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.
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