The effects of acute 17beta-estradiol treatment on gene expression in the young female mouse hippocampus.
The effects of acute 17beta-estradiol treatment on gene expression in the young female mouse hippocampus.
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DOI：
10.1016/j.nlm.2008.09.017
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发表时间：
2009-03
影响因子：
2.7
通讯作者：
Frick, Karyn M.
中科院分区：
文献类型：
--
作者：
Pechenino, Angela S.;Frick, Karyn M.
先前的研究表明，用17β-雌二醇（E2）治疗可以改善年轻雌性小鼠的空间和非空间记忆。然而，E2对记忆有益作用的分子机制尚不清楚。我们之前已经证明，训练后单次腹腔注射0.2 mg/kg E2可以增强海马依赖的空间和物体记忆巩固（例如，）。因此，在本研究中，我们对4月龄雌性小鼠海马背侧进行了微阵列分析，腹腔注射了载药或0.2 mg/kg E2。如果基因在E2治疗后显示RNA表达水平的变化大于对照组的两倍，则认为它们存在差异表达。总的来说，在大约25000个基因中，204个基因在E2处理后mRNA表达水平发生改变，其中111个基因表达上调，93个基因表达下调。其中，17个上调基因和6个下调基因与学习和记忆有关。实时定量PCR分析证实了5个基因的mRNA表达变化，Western blot分析证实了这些基因的蛋白变化：Hsp70，一种已知对雌激素有反应的热休克蛋白；igf - 1结合蛋白Igfbp2；Actn4，一种参与蛋白质运输的肌动蛋白结合蛋白；微管的主要成分Tubb2a；Snap25，一种神经递质释放所需的突触体特异性蛋白质。基因类型的改变表明E2可能诱导海马背侧细胞结构机制的改变，这可能有助于促进记忆巩固。
Previous studies have demonstrated that treatment with 17β-estradiol (E2) improves both spatial and nonspatial memory in young female mice. Still unclear, however, are the molecular mechanisms underlying the beneficial effects of E2 on memory. We have previously demonstrated that a single post-training intraperitoneal (i.p.) injection of 0.2 mg/kg E2 can enhance hippocampal-dependent spatial and object memory consolidation (e.g.,). Therefore, in the present study, we performed a microarray analysis on the dorsal hippocampi of 4 month-old female mice injected i.p. with vehicle or 0.2 mg/kg E2. Genes were considered differentially expressed following E2 treatment if they showed a greater than two-fold change in RNA expression levels compared to controls. Overall, out of a total of approximately 25,000 genes represented on the array, 204 genes showed altered mRNA expression levels upon E2 treatment, with 111 up-regulated and 93 down-regulated. Of these, 17 of the up-regulated and 6 of the down-regulated genes are known to be involved in learning and memory. mRNA expression changes in 5 of the genes were confirmed by real-time quantitative PCR analysis, and protein changes in these same genes were confirmed by Western blot analysis: Hsp70, a heat shock protein known to be estrogen responsive; Igfbp2, an IGF-I binding protein; Actn4, an actin binding protein involved in protein trafficking; Tubb2a, the major component of microtubules; and Snap25, a synaptosome-specific protein required for neurotransmitter release. The types of genes altered indicate that E2 may induce changes in the structural mechanics of cells within the dorsal hippocampus that could be conducive to promoting memory consolidation.
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