Gibbs R B
Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, 1004 Salk Hall, Pittsburgh, PA 15261, USA. gibbsr+@pitt.edu
Neurobiol Aging. 2000 Jan-Feb;21(1):107-16. doi: 10.1016/s0197-4580(00)00103-2.
Female Sprague-Dawley rats were ovariectomized at 13 months of age. Four groups received different regimens of estrogen or estrogen plus progesterone replacement beginning either immediately, 3 months, or 10 months after ovariectomy and were compared with non-hormone-treated controls. Eight to twelve months after ovariectomy, animals were trained on a delayed matching-to-position (DMP) spatial memory task. Long-term treatment with estrogen or estrogen plus progesterone significantly enhanced acquisition of the DMP task by aged animals after long-term loss of ovarian function. Weekly administration of estrogen and progesterone was at least as effective as, if not more effective than, continuous treatment with estrogen alone. In addition, treatment initiated 3 months, but not 10 months, after ovariectomy was as effective at enhancing DMP acquisition as continuous estrogen treatment initiated immediately after ovariectomy, suggesting a window of opportunity after the loss of ovarian function during which hormone replacement can effectively prevent the effects of aging and hormone deprivation on cognitive function. These findings suggest that repeated treatment with estrogen and progesterone initiated within a specific period of time after the loss of ovarian function may be effective at preventing specific negative effects of hormone deprivation on brain aging and cognitive decline.
13月龄的雌性斯普拉格-道利大鼠接受了卵巢切除术。四组大鼠在卵巢切除术后立即、3个月或10个月开始接受不同方案的雌激素或雌激素加孕激素替代治疗，并与未接受激素治疗的对照组进行比较。卵巢切除术后8至12个月，对动物进行延迟位置匹配（DMP）空间记忆任务训练。在长期丧失卵巢功能后，长期使用雌激素或雌激素加孕激素治疗可显著增强老龄动物对DMP任务的习得。每周给予雌激素和孕激素的效果至少与单独持续使用雌激素一样有效，甚至可能更有效。此外，在卵巢切除术后3个月而非10个月开始治疗，在增强DMP习得方面与卵巢切除术后立即开始的持续雌激素治疗效果相同，这表明在卵巢功能丧失后的一个机会窗口期内，激素替代可以有效预防衰老和激素缺乏对认知功能的影响。这些发现表明，在卵巢功能丧失后的特定时间段内开始重复使用雌激素和孕激素治疗，可能有效预防激素缺乏对脑衰老和认知衰退的特定负面影响。
