Estrogen synthesis in the brain - Role in synaptic plasticity and memory
Estrogen synthesis in the brain - Role in synaptic plasticity and memory
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DOI：
10.1016/j.mce.2008.04.017
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发表时间：
2008-08-13
影响因子：
4.1
通讯作者：
Kawato, Suguru
中科院分区：
文献类型：
--
作者：
Hojo, Yasushi;Murakami, Gen;Kawato, Suguru
雌激素和雄激素是由成年动物海马神经元局部的胆固醇合成的。这些神经类固醇由细胞色素P450和羟基类固醇脱氢酶（HSDs）和5 α-还原酶合成。酶的表达水平低至内分泌器官中的1/200-1/50，000，然而这些数字对于局部合成来说足够高。P450（17 α）、P450 arom、17 β-HSD和5 α-还原酶定位于海马CA 1、CA 3和齿状回的主要多巴胺能神经元。在海马中观察到几纳摩尔水平的雌激素和雄激素。雌激素不仅缓慢而且快速地调节海马中与记忆相关的突触可塑性。17 β-雌二醇通过膜受体的快速作用被证明用于棘发生和长期抑制（LTD）。1- 10 nM雌二醇对LTD的增强作用发生在1h内。应用雌二醇后2 h内，CA 1锥体神经元棘密度增加。然而，在CA 3锥体神经元中，雌二醇降低了棘样结构的密度。ER α（而非ER β）对脊髓发生和LTD均诱导相同的增强/抑制作用。（C）2008 Elsevier爱尔兰有限公司。保留所有权利。
Estrogen and androgen are synthesized from cholesterol locally in hippocampal neurons of adult animals. These neurosteroids are synthesized by cytochrome P450s and hydroxysteroid dehydrogenases (HSDs) and 5alpha-reductase. The expression levels of enzymes are as low as 1/200-1/50,000 of those in endocrine organs, however these numbers are high enough for local synthesis. Localization of P450(17alpha), P450arom, 17beta-HSD and 5alpha-reductase is observed in principal glutamatergic neurons in CA1, CA3 and the dendate gyrus. Several nanomolar levels of estrogen and androgen are observed in the hippocampus.Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. Rapid action of 17beta-estradiol via membrane receptors is demonstrated for spinogenesis and long-term depression (LTD). The enhancement of LTD by 1-10nM estradiol occurs within I h. The density of spine is increased in CA1 pyramidal neurons within 2 h after application of estradiol. The density of spine-like structure is, however, decreased by estradiol in CA3 pyramidal neurons. ERalpha, but not ERbeta, induces the same enhancement/suppression effects on both spinogenesis and LTD. (C) 2008 Elsevier Ireland Ltd. All rights reserved.