Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation
Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation
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DOI：
10.1210/en.2005-0998
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Berbling, JL
中科院分区：
文献类型：
--
作者：
Daniel, JM;Hulst, JL;Berbling, JL
本研究的目的是探索长期剥夺激素对随后雌激素替代影响认知的能力的影响。12月龄雌性大鼠接受卵巢切除(n=30)或假手术(n=10)。正常大鼠和20只去卵巢大鼠接受胆固醇植入。10只去卵巢大鼠接受含有25%雌二醇的埋植剂。五个月后，植入物被更换。卵巢切除后植入胆固醇的大鼠中，一半接受了雌二醇植入，另一半接受了新的胆固醇植入。植入雌二醇的大鼠接受了新的雌二醇植入物。正常大鼠摘除卵巢后植入雌二醇。从1wk后开始，在24天的八臂径向迷宫中以及在第四和第五臂选择之间施加2.5h延迟的另外八次试验中，对工作记忆的表现进行评估。与对照治疗相比，在12个月或17个月大的卵巢切除后立即开始雌激素替代显著改善了获取和延迟试验中的表现。当17个月龄，即卵巢切除后5个月开始雌激素替代时，没有明显的增强作用。接受延迟雌激素替代的大鼠子宫重量明显高于去卵巢对照组，但明显小于立即接受雌激素替代的大鼠。子宫重量与获取过程中的平均误差呈负相关。这些结果表明，虽然在卵巢切除后立即开始的长期雌激素替代方案对中年动物的工作记忆有积极的影响，但在长期激素剥夺后开始的雌激素替代方案并不有效。
The goal of the present study was to explore the effects of long-term hormone deprivation on the ability of subsequent estrogen replacement to affect cognition. Female rats, 12 months of age, underwent ovariectomies (n = 30) or sham surgeries (n = 10). Intact rats and 20 ovariectomized rats received cholesterol implants. Ten ovariectomized rats received implants containing 25% estradiol. Five months later, implants were replaced. Half of the ovariectomized rats with cholesterol implants received estradiol implants and half received new cholesterol implants. Rats with estradiol implants received new estradiol implants. Intact rats were ovariectomized and given estradiol implants. Beginning 1 wk later, working memory performance was assessed in an eight-arm radial maze across 24 d of acquisition and during eight additional trials in which a 2.5-h delay was imposed between the fourth and fifth arm choices. Estradiol replacement initiated immediately after ovariectomy at either 12 or 17 months of age significantly improved performance during acquisition and delay trials, compared with control treatment. When estradiol replacement was initiated at 17 months of age, 5 months after ovariectomy, no enhancements were evident. Uteri of rats that experienced delayed estradiol replacement weighed significantly more than uteri of ovariectomized controls but significantly less than uteri of rats that received immediate estradiol replacement. Uterine weight negatively correlated with mean errors during acquisition. These results indicate that whereas chronic estradiol replacement regimens positively affect working memory in middle-aged animals when initiated immediately after ovariectomy, estradiol replacement is not effective when initiated after long-term hormone deprivation.