Direct and indirect effects of estrogen on rat hippocampus
Direct and indirect effects of estrogen on rat hippocampus
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DOI：
10.1016/j.neuroscience.2005.05.061
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Rune, GM
中科院分区：
文献类型：
--
作者：
Prange-Kiel, J;Rune, GM
雌激素诱导的突触可塑性经常表现为增加棘CA1锥体神经元的顶树突后，全身应用雌二醇卵巢切除大鼠。最近的研究结果质疑雌二醇对突触发生的直接内分泌调节。我们已经表明，第一次，雌激素是在大鼠海马神经元从头合成。通过使用芳香酶抑制剂来曲唑，海马分散培养物和海马切片培养物中的雌二醇水平被显着抑制。来曲唑处理导致棘和棘突触的密度和突触前终扣的数量显著减少。定量免疫组化显示，剂量依赖性下调的亲棘素，脊髓标记物，和突触素，突触前标记物，在海马。令人惊讶的是，外源性应用雌二醇的文化没有影响。通过皮质下核团介导的雌激素的间接作用可能有助于解释这种现象。将雌激素填充的插管植入中缝正中，其投射到海马，导致治疗7天后海马中的棘密度显著增加。这种增加被CA1区的腔隙层和放射层的多巴胺能神经支配密度的降低所抵消。除了直接的内分泌机制，我们的研究结果表明，雌二醇诱导的海马棘也介导的间接机制，并进一步调节内源性，在旁分泌的方式。(C)2005由Elsevier Ltd代表IBRO出版。
Estrogen-induced synaptic plasticity was frequently shown by an increase of spines at apical dendrites of CA1 pyramidal neurons after systemic application of estradiol to ovariectomized rats. Recent findings question this direct endocrine regulation of synaptogenesis by estradiol. We have shown, for the first time, that estrogens are synthesized de novo in rat hippocampal neurons. By using letrozole, an inhibitor of aromatase, estradiol levels in hippocampal dispersion cultures as well as in hippocampal slice cultures were significantly suppressed. Letrozole treatment resulted in a significant decrease in the density of spines and spine synapses and in the number of presynaptic boutons. Quantitative immunohistochemistry revealed a dose-dependent downregulation of spinophilin, a spine marker, and of synaptophysin, a presynaptic marker, in the hippocampus. Surprisingly, exogenous application of estradiol to the cultures had no effect. Indirect effects of estrogens, mediated via subcortical nuclei, may help to explain this phenomenon. Implantation of estrogen-filled cannulae into the median raphe, which projects to the hippocampus, resulted in a significant increase in spine density in the hippocampus after seven days of treatment. This increase was paralleled by a decrease in the density of serotonergic innervation of the strata lacunosum moleculare and radiatum of the CA1 region. Apart from direct endocrine mechanisms our findings suggest that estradiol-induced spinogenesis in the hippocampus is also mediated by indirect mechanisms and is furthermore regulated endogenously, in a paracrine manner. (C) 2005 Published by Elsevier Ltd on behalf of IBRO.