期刊
HIPPOCAMPUS
卷 25, 期 12, 页码 1556-1566出版社
WILEY-BLACKWELL
DOI: 10.1002/hipo.22475
关键词
estrogen; estrogen receptor alpha and beta; GPR30; GPER1; estradiol; G1; G15; hippocampus; synaptic plasticity; ERK
资金
- National Institutes of Aging [R01AG037984, R37AG036800]
- Evelyn F. McKnight Brain Research Foundation
Estradiol rapidly modulates hippocampal synaptic plasticity and synaptic transmission; however, the contribution of the various estrogen receptors to rapid changes in synaptic function is unclear. This study examined the effect of estrogen receptor selective agonists on hippocampal synaptic transmission in slices obtained from 3-5-month-old wild type (WT), estrogen receptor alpha (ER alpha KO), and beta (ER beta KO) knockout female ovariectomized mice. Hippocampal slices were prepared 10-16 days following ovariectomy and extracellular excitatory postsynaptic field potentials were recorded from CA3-CA1 synaptic contacts before and following application of 17 beta-estradiol- 3-benzoate (EB, 100 pM), the G-protein estrogen receptor 1 (GPER1) agonist G1 (100 nM), the ER alpha selective agonist propyl pyrazole triol (PPT, 100 nM), or the ER beta selective agonist diarylpropionitrile (DPN, 1 mu M). Across all groups, EB and G1 increased the synaptic response to a similar extent. Furthermore, prior G1 application occluded the EB-mediated enhancement of the synaptic response and the GPER1 antagonist, G15 (100 nM), inhibited the enhancement of the synaptic response induced by EB application. We confirmed that the ERa and ERb selective agonists (PPT and DPN) had effects on synaptic responses specific to animals that expressed the relevant receptor; however, PPT and DPN produced only a small increase in synaptic transmission relative to EB or the GPER1 agonist. We demonstrate that the increase in synaptic transmission is blocked by inhibition of extracellular signal-regulated kinase (ERK) activity. Furthermore, EB was able to increase ERK activity regardless of genotype. These results suggest that ERK activation and enhancement of synaptic transmission by EB involves multiple estrogen receptor subtypes. (C) 2015 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据