Estradiol and the relationship between dendritic spines, NR2B containing NMDA receptors, and the magnitude of long-term potentiation at hippocampal CA3-CA1 synapses.
Estradiol and the relationship between dendritic spines, NR2B containing NMDA receptors, and the magnitude of long-term potentiation at hippocampal CA3-CA1 synapses.
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DOI：
10.1016/j.psyneuen.2009.06.003
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发表时间：
2009-12
影响因子：
3.7
通讯作者：
McMahon, Lori L
中科院分区：
文献类型：
--
作者：
Smith, Caroline C;Vedder, Lindsey C;McMahon, Lori L
当循环雌激素水平下降作为一个自然的结果更年期和衰老的妇女，有一个增加的发病率赤字的工作记忆。在许多情况下，这些缺陷可以通过雌激素替代疗法来挽救。因此，这些临床数据强调了确定雌激素与学习和记忆的细胞基质之间的生物学途径的重要性。近二十年来，人们已经知道雌激素增强海马CA 1锥体细胞顶端树突上的树突棘密度，海马是学习所需的大脑区域。有趣的是，在CA 3-CA 1锥体细胞之间的突触处，雌激素也被证明能增强突触NMDA受体电流和长时程增强的幅度，这是一种与学习和记忆相关的细胞。考虑到海马中CA 3-CA 1突触的突触密度、NMDAR功能和长时程增强与正常学习相关，雌激素对这些参数的调节可能有助于在雌激素替代后大鼠、灵长类动物和人类中观察到的学习改善。为了促进临床策略的设计，以潜在地防止或扭转更年期的学习和记忆的年龄相关的下降，雌激素诱导的海马形态和功能的变化之间的关系必须被定义和这些变化在促进学习中发挥的作用必须被阐明。本报告的目的是提供一个总结的建议，这种激素增加突触功能的机制，并在这样做，它简要地解决了潜在的机制，有助于雌激素诱导的突触形态和可塑性的增加，以及重要的未来方向。
When circulating estrogen levels decline as a natural consequence of menopause and aging in women, there is an increased incidence of deficits in working memory. In many cases, these deficits are rescued by estrogen replacement therapy. These clinical data therefore highlight the importance of defining the biological pathways linking estrogen to the cellular substrates of learning and memory. It has been known for nearly two decades that estrogen enhances dendritic spine density on apical dendrites of CA1 pyramidal cells in hippocampus, a brain region required for learning. Interestingly, at synapses between CA3-CA1 pyramidal cells, estrogen has also been shown to enhance synaptic NMDA receptor current and the magnitude of long term potentiation, a cellular correlate of learning and memory. Given that synapse density, NMDAR function, and long term potentiation at CA3-CA1 synapses in hippocampus are associated with normal learning, it is likely that modulation of these parameters by estrogen facilitates the improvement in learning observed in rats, primates and humans following estrogen replacement. To facilitate the design of clinical strategies to potentially prevent or reverse the age-related decline in learning and memory during menopause, the relationship between the estrogen-induced morphological and functional changes in hippocampus must be defined and the role these changes play in facilitating learning must be elucidated. The aim of this report is to provide a summary of the proposed mechanisms by which this hormone increases synaptic function and in doing so, it briefly addresses potential mechanisms contributing to the estrogen-induced increase in synaptic morphology and plasticity, as well as important future directions.