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雌激素在背侧海马体中作用的新靶点:对突触蛋白的研究

Novel target sites for estrogen action in the dorsal hippocampus: an examination of synaptic proteins.

作者信息

Brake W G, Alves S E, Dunlop J C, Lee S J, Bulloch K, Allen P B, Greengard P, McEwen B S

机构信息

Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021, USA.

出版信息

Endocrinology. 2001 Mar;142(3):1284-9. doi: 10.1210/endo.142.3.8036.

DOI:10.1210/endo.142.3.8036
PMID:11181546
Abstract

Structural studies have shown that estrogens increase dendritic spine number in the dorsal CA1 field of rat hippocampus using Golgi impregnation as well as the number of dorsal CA1 synapses visualized via electron microscopy. The present study was carried out to further these findings by examining changes in the levels of pre- and postsynaptic proteins using radioimmunocytochemistry (RICC). In this study, 2 days of estradiol-benzoate treatment produced significant and comparable increases in synaptophysin, syntaxin, and spinophilin immunoreactivity (IR) in the CA1 region of the dorsal hippocampus of ovariectomized female rats. For spinophilin, IR was also increased in the hilar region of the dentate gyrus as well as CA3. In all cases, the nonsteroidal estrogen antagonist CI628, which has been previously shown to block spine formation, inhibited the effects of estrogen. However, these protein differences were not detected in whole hippocampus using Western blots. These findings add to a growing body of evidence that estrogens increase synapses in the CA1 region of hippocampus along with changes in previously unidentified sites. These results also suggest that RICC is a rapid and sensitive method for examining molecular changes in synaptic profiles in anatomically distinct brain regions.

摘要

结构研究表明,使用高尔基染色法发现雌激素可增加大鼠海马背侧CA1区的树突棘数量,通过电子显微镜观察也发现雌激素可增加背侧CA1区的突触数量。本研究通过放射免疫细胞化学(RICC)检测突触前和突触后蛋白水平的变化,以进一步证实这些发现。在本研究中,对去卵巢雌性大鼠的背侧海马CA1区进行两天的苯甲酸雌二醇处理后,突触素、 syntaxin和棘状蛋白的免疫反应性(IR)显著且相当程度地增加。对于棘状蛋白,齿状回门区以及CA3区的IR也增加。在所有情况下,先前已证明可阻断脊柱形成的非甾体雌激素拮抗剂CI628可抑制雌激素的作用。然而,使用蛋白质印迹法在整个海马中未检测到这些蛋白质差异。这些发现进一步证明,雌激素会增加海马CA1区的突触数量,并伴随先前未确定部位的变化。这些结果还表明,RICC是一种快速且灵敏的方法,可用于检测解剖学上不同脑区突触轮廓的分子变化。

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