Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance.
Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance.
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DOI：
10.1016/j.psyneuen.2009.01.004
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发表时间：
2009-07
影响因子：
3.7
通讯作者：
Frye, Cheryl A.
中科院分区：
文献类型：
--
作者：
Walf, Alicia A.;Paris, Jason J.;Frye, Cheryl A.
随着更年期的过渡，卵巢类固醇雌二醇 (E2) 的下降可能会影响老年女性的认知和情感处理，并且有证据表明，使用 E2 模拟物的激素替代疗法 (HRT) 可能对某些（但不是全部）女性有益。在确定 HRT 反应是否积极方面发挥作用的参数令人感兴趣。积极反应的可能性可能与 E2 下降后更换 E2 的时间有关。因此，在本研究中，利用动物模型来对此进行研究。我们通过检查雌性大鼠的认知（物体放置任务）、焦虑（开放场、镜子迷宫、明暗转换任务）和抑郁（强迫游泳任务）行为来研究长期与短期E2替代的影响，这些雌性大鼠在中年（14个月）或以上（19个月）切除卵巢（OVX）并在手术时或延迟5个月后植入E2填充植入物，或在14个月大时进行OVX且从未植入替换为E2。大鼠在 20 个月大时进行了测试。测试的假设是，与延迟 E2 替代相比，在卵巢终止时替代 E2 可以减少大鼠的焦虑和抑郁行为，并改善认知表现。与 OVX 和连续施用安慰剂载体的大鼠相比，OVX 然后接受连续 E2 替代的大鼠在物体放置任务中的表现得到改善。在旷场和强迫游泳任务中，与给予赋形剂或延迟 E2 替代的 OVX 大鼠相比，OVX 然后接受连续 E2 替代的大鼠的抗焦虑和抗抑郁行为分别有所增加。在镜子迷宫和明暗转换任务中，在 OVX 或延迟后更换 E2，减少了焦虑样行为。因此，E2 替代减少了老年雌性大鼠的焦虑和抑郁行为，并改善了认知表现；然而，E2治疗的延迟影响了E2在某些任务中是否有有利的效果。
Decline in the ovarian steroid, estradiol (E2), with the menopause transition may influence cognitive and affective processing of older women and there is evidence that hormone replacement therapies (HRTs) with E2-mimetics may provide benefit in some, but not all, women. The parameters that play a role in determining whether the response to HRTs is positive are of interest. It may be that the likelihood for positive responses is related to the timing of E2-replacement following E2 decline. As such, in the present study an animal model was utilized to investigate this. We investigated the effects of long- vs. short-term E2 replacement by examining cognitive (object placement task), anxiety (open field, mirror maze, light-dark transition task), and depression (forced swim task) behavior of female rats that were ovariectomized (OVX) at middle-age (14 months) or older (19 months) and implanted with E2–filled implants at the time of surgery or after a delay of 5 months, or OVX at 14 months of age and never replaced with E2. Rats were tested at 20 months of age. The hypothesis that was tested was that rats would have reduced anxiety and depression behavior and improved cognitive performance with E2-replacement at ovarian cessation, compared to with a delay in E2-replacement. Performance in the object placement task was improved in rats that were OVX and then received continuous E2-replacement, compared to those that were OVX and continuously administered placebo vehicle. In the open field and forced swim task, there was an increase in anti-anxiety and anti-depressive behavior, respectively, among rats that were OVX and then received continuous E2-replacement, compared to OVX rats administered vehicle or those that experienced a delay in E2 replacement. In the mirror maze and light-dark transition task, E2-replacement at OVX, or after a delay, reduced anxiety-like behavior. Thus, E2 replacement reduced anxiety and depression behavior and improved cognitive performance of aged female rats; however, delay in E2 treatment influenced whether there were favorable effects of E2 in some tasks.
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3.5
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