Acute effects of 17β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats

Acute effects of 17β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats
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DOI:
10.1007/s11357-010-9148-6
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发表时间:
2010-12-01
期刊:
AGE
影响因子:
--
通讯作者:
Gonzalez, Celestino
Gonzalez, Celestino
中科院分区:
医学2区
文献类型:
--
作者:
Alonso, Ana;Gonzalez-Pardo, Hector;Gonzalez, Celestino

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衰老的特征是代谢功能下降和胰岛素抵抗,两者似乎都是神经退行性疾病和认知功能障碍的基础。雌激素可以防止与年龄有关的变化,植物雌激素影响学习和记忆。我们的假设是,雌二醇和染料木黄酮,使用快速作用机制,能够修改胰岛素敏感性,学习过程和空间记忆。年轻和老年卵巢切除大鼠接受急性治疗与雌二醇或染料木素。老年动物比年轻动物更耐胰岛素。在每个年龄,雌二醇和染料木黄酮治疗的动物比其他动物的胰岛素抵抗,除了在年轻的动物与高剂量的染料木黄酮治疗的情况下。老年大鼠在空间记忆测试中没有发现组间差异,在水迷宫任务中表现较差。而雌激素组和高剂量金雀异黄素组在空间记忆任务中的表现与对照组相似。只有接受高剂量染料木黄酮治疗的大鼠表现出与对照组相似的最佳空间记忆。相反,高剂量植物雌激素的急性治疗仅在幼鼠中改善了空间记忆巩固,支持了雌激素对记忆有益作用的关键期假说。因此,金雀异黄素治疗似乎是合适的治疗在老年大鼠,以防止胰岛素抵抗,但不是记忆衰退与老化。急性染料木黄酮治疗不能有效地恢复与卵巢功能早期丧失相关的胰岛素抵抗,尽管它可以改善这种情况下的记忆缺陷。
Aging is characterized by decline in metabolic function and insulin resistance, and both seem to be in the basis of neurodegenerative diseases and cognitive dysfunction. Estrogens prevent age-related changes, and phytoestrogens influence learning and memory. Our hypothesis was that estradiol and genistein, using rapid-action mechanisms, are able to modify insulin sensitivity, process of learning, and spatial memory. Young and aged ovariectomized rats received acute treatment with estradiol or genistein. Aged animals were more insulin-resistant than young. In each age, estradiol and genistein-treated animals were less insulin-resistant than the others, except in the case of young animals treated with high doses of genistein. In aged rats, no differences between groups were found in spatial memory test, showing a poor performance in the water maze task. However, young females treated with estradiol or high doses of genistein performed well in spatial memory task like the control group. Only rats treated with high doses of genistein showed an optimal spatial memory similar to the control group. Conversely, acute treatment with high doses of phytoestrogens improved spatial memory consolidation only in young rats, supporting the critical period hypothesis for the beneficial effects of estrogens on memory. Therefore, genistein treatment seems to be suitable treatment in aged rats in order to prevent insulin resistance but not memory decline associated with aging. Acute genistein treatment is not effective to restore insulin resistance associated to the early loss of ovarian function, although it can be useful to improve memory deficits in this condition.