The 17α and 17β isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats
The 17α and 17β isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats
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DOI：
10.1210/en.2004-0730
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发表时间：
2005-01-01
期刊：
影响因子：
4.8
通讯作者：
Leranth, C
中科院分区：
文献类型：
--
作者：
MacLusky, NJ;Luine, VN;Leranth, C
先前的研究表明，雌二醇-17 β和雌二醇-17 α都能诱导大鼠空间记忆的短潜伏期效应，雌二醇-17 α至少与其17 β异构体一样有效。为了确定这些行为反应的潜在机制是否可能包括对海马突触可塑性的影响，在皮下注射雌激素后的最初几个小时内测量卵巢切除大鼠的CA 1锥体棘突触密度（PSSD）。在给予45 μ g/kg雌二醇-17 β后4.5小时，PSSD显著增加（增加24%）。注射雌二醇-17 β后30分钟，PSSD反应显著更大（比对照组高44%），并且具有明显的剂量依赖性;雌二醇-17 β剂量降低3倍（15 μ g/kg）在30分钟或4.5小时对CA 1 PSSD没有显著影响。雌二醇-17 α是比雌二醇-17 β更有效的PSSD诱导剂。剂量反应分析确定雌二醇-17 α对PSSD作用的ED 50为8.92+/-1.99 mug/kg，最大反应为15 mug/kg。这些结果表明，高剂量的雌二醇诱导CA 1 PSSD的快速变化。CA 1棘突触的形成似乎是更敏感的雌二醇-17 α比雌二醇-17 β，平行于以前的数据，这两种类固醇对空间记忆的影响。因此，海马突触连接的快速重塑可能有助于雌激素治疗后最初几个小时内观察到的空间记忆处理的增强。雌二醇-17 α的效力表明，使用这种类固醇的激素替代疗法在临床上可能有助于改善低内源性雌激素产生对涉及海马的神经退行性疾病的发展和进展的影响。
Previous studies have demonstrated that estradiol-17beta and estradiol-17alpha both induce short-latency effects on spatial memory in rats, estradiol-17alpha being at least as potent as its 17beta isomer. To determine whether the mechanisms underlying these behavioral responses might include effects on hippocampal synaptic plasticity, CA1 pyramidal spine synapse density (PSSD) was measured in ovariectomized rats within the first few hours after sc estrogen injection. PSSD increased markedly (by 24%) 4.5 h after the administration of 45 mug/kg estradiol-17beta. The PSSD response was significantly greater (44% above control) 30 min after estradiol-17beta injection and was markedly dose dependent; a 3-fold lower estradiol-17beta dose (15 mug/kg) did not significantly affect CA1 PSSD at either 30 min or 4.5 h. Estradiol-17alpha was a more potent inducer of PSSD than estradiol-17beta. Dose-response analysis determined an ED50 for the effect of estradiol-17alpha on PSSD of 8.92+/-1.99 mug/kg, with a maximal response at 15 mug/kg. These results demonstrate that high doses of estradiol induce rapid changes in CA1 PSSD. CA1 spine synapse formation appears to be more sensitive to estradiol-17alpha than to estradiol-17beta, paralleling previous data on the effects of these two steroids on spatial memory. Rapid remodeling of hippocampal synaptic connections may thus contribute to the enhancement of spatial mnemonic processing observed within the first few hours after estrogen treatment. The potency of estradiol-17alpha suggests that hormone replacement therapy using this steroid might be useful clinically in ameliorating the impact of low endogenous estrogen production on the development and progression of neurodegenerative disorders involving the hippocampus.