N-methyl-D-aspartate receptor mRNA levels change during reproductive senescence in the hippocampus of female rats
N-methyl-D-aspartate receptor mRNA levels change during reproductive senescence in the hippocampus of female rats
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DOI：
10.1006/exnr.2001.7687
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发表时间：
2001-07-01
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;Morrison, JH;Gore, AC
雌激素与N-甲基-D-天冬氨酸(NMDA)受体相互作用，调节形态和功能可塑性的多个方面。在海马区，雌激素增加树突棘密度和突触数量，NMDA拮抗剂可以阻断这些作用。在雌激素水平变化和认知功能经常受损的衰老背景下，这种由雌激素介导的海马区可塑性可能特别重要。因此，本研究旨在探讨衰老和生殖状况对大鼠海马神经元NMDA受体(NR)亚单位mRNA水平的影响。用核糖核酸酶保护法测定了青年(3~4月龄)、中年(12~13月龄)和老年(24~25月龄)SD大鼠动情周期不同阶段的NR1、MR2A和NR2B基因表达水平。我们的结果表明，NMDA受体亚单位的mRNA水平受年龄的影响比受动物的生殖状况的影响更大。腹侧海马区NR1、NR2a、NR2B和背侧海马区NR1、NR2B与年龄相关。然而，与生殖状态有关的只有NR1mRNA，而且这种关系仅限于腹侧海马区。年龄段和生殖状态之间存在交互作用，发情前期幼年动物的NR1mRNA水平高于发情间期幼年动物(分别为高雌激素水平和低雌激素水平)。然而，这种关系在老年受试者中未见。这些结果表明，海马区NMDA受体亚单位mRNA水平受到年龄相关的改变，不同年龄的动物受到生殖状况的不同影响。NMDA受体mRNA水平的这种变化可能是导致正常衰老过程中认知行为改变的一个可能的分子机制。(C)2001年学术出版社。
Estrogen interacts with N-methyl-D-aspartate (NMDA) receptors to regulate multiple aspects of morphological and functional plasticity. In the hippocampus, estrogens increase both dendritic spine density and synapse number, and NMDA antagonists block these effects. This plasticity in the hippocampus mediated by estrogen may be of particular importance in the context of aging when estrogen levels change and cognitive function is often impaired. Therefore, the present study was designed to investigate effects of aging and reproductive status on NMDA receptor (NR) subunit mRNA levels in the hippocampus. NR1, MR2A, and NR2B mRNA levels were measured by RNase protection assay in young (3-4 month), middle-aged (12-13 month), and aged (24-25 month) Sprague-Dawley rats in different phases of the estrous cycle in cycling animals and in acyclic subjects. Our results demonstrated that NMDA receptor subunit mRNA levels were much more prominently affected by the chronological age than by the reproductive status of the animals. Age-related changes were observed in NR1, NR2A, and NR2B in the ventral hippocampus and in NR1 and NR2B in the dorsal hippocampus. However, the only relationship with reproductive status was seen for NR1 mRNA, and this was restricted to the ventral hippocampus. An interaction between chronological age and reproductive status was found, with higher levels of NR1 mRNA seen in young animals in proestrus than in those in diestrus I (high and low estrogen levels, respectively). However, this relationship was not seen in the aged subjects. These results demonstrate that the hippocampus is subjected to age-related alterations in NMDA receptor subunit mRNA levels and that animals of different ages are influenced differently by reproductive status. This shift in the NMDA receptor mRNA levels may be a possible molecular mechanism contributing to alterations in cognitive behavior during normal aging. (C) 2001 Academic Press.