Length of postovariectomy interval and age, but not estrogen replacement, regulate N-methyl-D-aspartate receptor mRNA levels in the hippocampus of female rats
Length of postovariectomy interval and age, but not estrogen replacement, regulate N-methyl-D-aspartate receptor mRNA levels in the hippocampus of female rats
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DOI：
10.1006/exnr.2001.7716
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发表时间：
2001-08-01
影响因子：
5.3
通讯作者：
Gore, AC
中科院分区：
文献类型：
--
作者：
Adams, MM;Oung, T;Gore, AC
雌激素和N -甲基- D -天冬氨酸（NMDA）受体调节幼龄动物形态和功能可塑性的多个方面。例如，雌激素可增加海马中的树突棘密度，而NMDA拮抗剂可阻断这些作用。很少有研究探讨年龄、卵巢切除后的间隔时间以及雌激素替代的持续时间对海马的影响，更具体地说是对NMDA受体亚单位的影响。因此，本研究旨在探讨短期和长期雌激素替代或剥夺对老龄雌性斯普拉格 - 道利大鼠海马中三种NMDA受体亚单位（NR1、NR2A和NR2B）mRNA水平的影响。将年轻（3 - 4月龄）和中年（12 - 13月龄）大鼠卵巢切除1个月，然后分别用雌激素或赋形剂处理2天或2周。另一组中年和老年（24 - 25月龄）动物卵巢切除6个月，并用雌激素或赋形剂处理2天或2周。采用核糖核酸酶保护试验评估NMDA受体亚单位mRNA水平的变化。我们的结果表明，年龄和卵巢切除时间对NMDA受体mRNA水平有显著影响，而动物的雌激素状态对这些参数影响较小。卵巢切除后间隔时间的长短影响最大，结果表明短期卵巢切除的大鼠其NMDA受体亚单位mRNA水平明显高于长期卵巢切除的动物。在腹侧海马中，NR1和NR2B mRNA随年龄增长的变化最为显著，呈现出与年龄相关的大幅增加。这些数据表明，年龄和卵巢切除持续时间影响海马中NMDA受体mRNA水平，可能影响这些受体的化学计量和/或功能。这些发现对人类绝经后或子宫切除/卵巢切除后的雌激素耗竭和替代具有重要意义。（C）2001学术出版社
Estrogens and N-methyl-D-aspartate (NMDA) receptors regulate multiple aspects of morphological and functional plasticity in young animals. For example, estrogens increase spine density in the hippocampus, and NMDA antagonists block these effects. Few studies have examined the effects of age, postovariectomy interval, and duration of estrogen replacement in the hippocampus and more specifically on NMDA receptor subunits. Therefore, the present study was designed to investigate the effects of short- and long-term estrogen replacement or deprivation on mRNA levels of three NMDA receptor subunits, NR1, NR2A, and NR2B, in the hippocampus of aging female Sprague-Dawley rats. Young (3- to 4-month-old) and middle-aged (12- to 13-month-old) rats were ovariectomized for 1 month and then treated with estrogen or vehicle for either 2 days or 2 weeks. Another set of middle-aged and aged (24-to 25-month-old) animals were ovariectomized for 6 months and treated with estrogen or vehicle for 2 days or 2 weeks. RNase protection assay was used to assess changes in the NMDA receptor subunit mRNA levels. Our results demonstrated significant effects of age and length of ovariectomy on NMDA receptor mRNA levels, with little effect of the estrogen status of the animals on these parameters. The largest effect was seen for the length of the postovariectomy interval, with the results demonstrating that rats with a short-term ovariectomy have substantially higher NMDA receptor subunit mRNA levels than animals with long-term ovariectomy. The most dramatic effects of aging were seen for NR1 and NR2B mRNAs in ventral hippocampus, with large age-related increases. These data suggest that age and duration of ovariectomy impact NMDA receptor mRNA levels in the hippocampus, potentially affecting the stoichiometry and/or function of these receptors. These findings have important implications for postmenopausal or hysterectomy/oophorectomy estrogen depletion and replacement in humans. (C) 2001 Academic Press.