Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton.
Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton.
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DOI：
10.1016/j.neuroscience.2012.10.038
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发表时间：
2013-06-03
期刊：
影响因子：
3.3
通讯作者：
Lynch, G.
中科院分区：
文献类型：
--
作者：
Kramar, E. A.;Babayan, A. H.;Gall, C. M.;Lynch, G.
雌激素的急性，易化作用的多巴胺能传输和长时程增强（LTP）提供了一个潜在的解释类固醇的相当大的影响行为。最近的工作已经确定了这些突触作用的机制。将17β-雌二醇（E2）短暂输注到成年雄性大鼠海马脑片中，通过从GTdR RhoA开始并以丝切断蛋白cofilin失活结束的信号级联反应触发树突棘内的肌动蛋白聚合。阻断这一序列或肌动蛋白聚合本身，消除了E2对突触生理学的影响。值得注意的是，用于诱导LTP的θ爆发刺激激活与E2相同的信号传导途径，加上稳定突触下细胞骨架重组的事件。这些观察结果表明，E2 elevelines的LTP的部分形式，导致快速EPSP的增加和持续突触变化的阈值降低。虽然E2对细胞骨架的影响可能是直接的，但本文描述的结果表明，该激素激活脑源性神经营养因子的突触TrkB受体，脑源性神经营养因子是一种可释放的神经营养因子，刺激RhoA至cofilin通路。因此，E2可能通过激活邻近受体来改变兴奋性接触的组成和结构。最后，还有一个问题是，急性突触活动的丧失是否会导致与雌激素耗尽相关的记忆问题。最初的测试发现，中年大鼠的卵巢切除术破坏了RhoA信号传导，肌动蛋白聚合和LTP巩固。E2的急性应用逆转了这些缺陷，这一结果与以下观点一致：肌动蛋白管理的干扰是伴随类固醇水平降低而出现的行为效应的原因之一。
Estrogen's acute, facilitatory effects on glutamatergic transmission and long-term potentiation (LTP) provide a potential explanation for the steroid's considerable influence on behavior. Recent work has identified mechanisms underlying these synaptic actions. Brief infusion of 17β-estradiol (E2) into adult male rat hippocampal slices triggers actin polymerization within dendritic spines via a signaling cascade beginning with the GTPase RhoA and ending with inactivation of the filament severing protein cofilin. Blocking this sequence, or actin polymerization itself, eliminates E2's effects on synaptic physiology. Notably, the theta burst stimulation used to induce LTP activates the same signaling pathway as E2 plus events that stabilize the reorganization of the sub-synaptic cytoskeleton. These observations suggest that E2 elicits a partial form of LTP, resulting in an increase of fast EPSP's and a reduction in the threshold for lasting synaptic changes. While E2's effects on the cytoskeleton could be direct, results described here indicate that the hormone activates synaptic TrkB receptors for Brain Derived Neurotrophic Factor, a releasable neurotrophin that stimulates the RhoA to cofilin pathway. It is therefore possible that E2 acts via transactivation of neighboring receptors to modify the composition and structure of excitatory contacts. Finally, there is the question of whether a loss of acute synaptic actions contributes to the memory problems associated with estrogen depletion. Initial tests found that ovariectomy in middle-aged rats disrupts RhoA signaling, actin polymerization, and LTP consolidation. Acute applications of E2 reversed these defects, a result consistent with the idea that disturbances to actin management are one cause of behavioral effects that emerge with reductions in steroid levels.
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影响因子：
3.5
作者：
Aenlle, Kristina K.;Foster, Thomas C.
通讯作者：
Foster, Thomas C.
DOI：
10.1111/j.1749-6632.2010.05529.x
发表时间：
2010-01-01
期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Devi, Gayatri;Hahn, Katherine;Zhivotovskaya, Emiliya
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