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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Duration of estrogen deprivation, not chronological age, prevents estrogen's ability to enhance hippocampal synaptic physiology
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Duration of estrogen deprivation, not chronological age, prevents estrogen's ability to enhance hippocampal synaptic physiology

机译：雌激素剥夺的持续时间（而不是年龄）会阻止雌激素增强海马突触生理的能力

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Whether estrogen replacement is beneficial to cognitive health is controversial. Some-studies have shown that estrogen replacement therapy (ERT) relieves memory impairment associated with menopause in women, whereas others suggest that estrogen not only is incapable of providing a benefit, but actually can be detrimental. One possible explanation for this discrepancy in study findings could be the varying time after menopause at which ERT is initiated. It has been proposed that a critical period exists during which ERT must be administered to enhance cognitive function. This idea has yet to be tested directly using functional synaptic studies, however. Here we investigated whether prolonged hormone deprivation caused by ovariectomy (OVX) in young adult rats prevents the ability of estrogen replacement to increase synaptic function in the hippocampus to a degree necessary for estrogen-induced improvement in learning and memory. Remarkably, estrogen replacement was found to increase long-term potentiation, the current mediated by NR2B-containing NMDA receptors, and the dendritic spine density at CA3-CA1 synapses up to 15 months post-OVX. However, by 19 months post-OVX, the same estrogen replacement was unable to induce these changes. Importantly, this loss of estrogen's effectiveness was seen to be a consequence of the duration of deprivation. In female rats aged with their ovaries intact and examined at the same chronological age as the 19-month post-OVX group, estrogen replacement significantly increased synaptic function and spine density. These data clearly demonstrate that a.critical period exists during which ERT must be administered, and that once this period passes, the beneficial effects are lost.
机译：雌激素替代是否有益于认知健康尚存争议。一些研究表明，雌激素替代疗法（ERT）可以缓解女性绝经相关的记忆障碍，而另一些研究表明，雌激素不仅不能提供益处，而且实际上可能有害。关于研究结果差异的一种可能的解释可能是更年期后开始ERT的时间不同。已经提出存在关键时期，在该关键时期必须进行ERT以增强认知功能。然而，这一想法尚未直接通过功能性突触研究得到检验。在这里，我们调查了由成年雌性大鼠卵巢切除术（OVX）引起的长时间激素剥夺是否能阻止雌激素替代物增加海马突触功能的能力，从而达到雌激素诱导的学习和记忆改善所必需的程度。值得注意的是，发现雌激素替代可增加长期增强作用，电流是由含NR2B的NMDA受体介导的，CA3-CA1处的树突棘密度在OVX后长达15个月会突触。但是，到OVX后19个月，相同的雌激素替代物无法诱导这些变化。重要的是，这种雌激素功效的丧失被认为是剥夺持续时间的结果。在卵巢完整且在与OVX后19个月组相同的年龄进行检查的雌性大鼠中，雌激素替代明显增加了突触功能和脊柱密度。这些数据清楚地表明，存在必须进行ERT的关键时期，并且一旦超过该时期，就会失去有益的作用。

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