Neuroprotective Role of Estradiol against Neuronal Death Induced by Glucose Deprivation in Cultured Rat Hippocampal Neurons
Neuroprotective Role of Estradiol against Neuronal Death Induced by Glucose Deprivation in Cultured Rat Hippocampal Neurons
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DOI：
10.1159/000334229
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发表时间：
2012-01-01
影响因子：
4.1
通讯作者：
Camacho-Arroyo, Ignacio
中科院分区：
文献类型：
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作者：
Hernandez-Fonseca, Karla;Massieu, Lourdes;Camacho-Arroyo, Ignacio
已有研究报道雌二醇(E-2)对缺氧、线粒体毒素和谷氨酸受体激活等多种损伤所致的神经元死亡有保护作用。葡萄糖剥夺(GD)与缺血和低血糖相关，到目前为止，还没有有效的治疗药物能够预防由这些条件引起的神经元损伤。在本研究中，我们观察了17β-E-2和雌激素受体α(ERα)和β(ERβ)选择性激动剂丙基吡唑三醇(PPT)和二芳基丙腈(DPN)对GD诱导的培养大鼠海马神经元死亡的影响。我们还分析了GD后两种ER异构体的表达情况。结果表明，GD作用2 h和4 h后，细胞存活率分别下降42%和55%。17β-E-2(10 nm~10 mM)可诱导剂量依赖性保护作用，该作用可分别被ER拮抗剂ICI182,780以及选择性ERα和ERβ拮抗剂1，3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(-piperidinylethoxy)phenol]-1H‘pyrazole digul盐酸盐和4-[2-phenyl-5，7-bis(trifluoromethyl)pyrazolo[1，5-a]pyrimidin-3-yl]phenol所阻断。ERα和ERβ激动剂PPT和DPN显示出与17β-E-2相似的神经保护作用，但DPN更有效。此外，正常情况下的海马神经元表现出较高的ERβ亚型表达。在GD作用4h内，两种ER亚型的表达均增加，而在GD作用2 h后，只有ERβ亚型的表达显著增加。结果表明，E-2通过与ER的相互作用来预防GD诱导的神经元死亡，尽管ERβ亚型可能起主导作用。结果还表明，GD对海马神经元ERα和ERβ的表达有不同程度的影响。版权所有(C)2011年S.Karger AG，巴塞尔
Studies have reported the protective effect of estradiol (E-2) against neuronal death induced by several insults including oxygen deprivation, mitochondrial toxins and activation of glutamate receptors. Glucose deprivation (GD) is associated with ischemia and hypoglycemia, and to date there is no effective therapeutic agent able to prevent neuronal damage induced by these conditions. In this study, we have investigated the effects of 17 beta-E-2 and the selective agonists of the alpha (ER alpha) and beta (ER beta) estrogen receptors, propyl pyrazole triol (PPT) and diarylpropionitrile (DPN), respectively, on neuronal death induced by GD in cultured rat hippocampal neurons. We have also analyzed the expression of both ER isoforms after GD. Results show that GD for 2 and 4 h reduces cell survival by 42 and 55%, respectively. Treatment with 17 beta-E-2 (10 nm to 10 mu m) induces a dose-dependent protective effect that is blocked by ICI 182,780, an ER antagonist, and by 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(-piperidinylethoxy)phenol]-1H'pyrazole dihydrochloride (MPP) and 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), selective ER alpha and ER beta antagonists, respectively. The ER alpha and ER beta agonists PPT and DPN show a similar neuroprotective effect to that of 17 beta-E-2, but DPN is more efficient. In addition, hippocampal neurons under normal conditions show a higher expression of the ER beta isoform. When exposed to GD during 4 h, the expression of both ER isoforms is increased, while only that of the ER beta isoform significantly increases after 2 h of GD. Results demonstrate that E-2 prevents neuronal death induced by GD through its interaction with ER, although the ER beta isoform might have a predominant role. Results also suggest that GD differentially alters the expression of ER alpha and ER beta in hippocampal neurons. Copyright (c) 2011 S. Karger AG, Basel