Rapid spinogenesis of pyramidal neurons induced by activation of glucocorticoid receptors in adult male rat hippocampus

Rapid spinogenesis of pyramidal neurons induced by activation of glucocorticoid receptors in adult male rat hippocampus
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DOI:
10.1016/j.bbrc.2005.07.173
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发表时间:
2005-10-07
影响因子:
3.1
通讯作者:
Kawato, S
Kawato, S
中科院分区:
生物学4区
文献类型:
--
作者:
Komatsuzaki, Y;Murakami, G;Kawato, S

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糖皮质激素对海马突触可塑性的调节因其在应激反应中的重要作用而备受关注。树突棘对记忆储存过程至关重要。本研究通过对注射了路西法黄的成年雄性大鼠海马树突棘的成片成像,研究了糖皮质激素受体(GR)特异性激动剂地塞米松(DEX)对树突棘密度和形态的影响。100 nM DEX(应激高浓度)在1 h内诱导CA1锥体神经元树突棘的密度和形态发生快速调节,总棘密度从对照组的0.88棘/ μ m增加到DEX处理组的1.36棘/ μ m。DEX显著增加了细刺和蘑菇型刺的密度,而对短棍型和丝状型刺的密度仅略有增加。由于10 μ M环己亚胺(一种蛋白质合成抑制剂)的存在并没有抑制DEX效应,这些反应可能是非基因组性的。Western免疫印迹分析显示经典型GR定位于海马体片的triton不溶性突触体部分(突触后膜富集),提示DEX可能作用于脊柱。(c) 2005爱思唯尔公司版权所有。
Modulation of hippocampal synaptic plasticity by glucocorticoids has been attracting much attention, due to its importance in stress responses. Dendritic spines are essential for memory storage processes. Here, we investigated the effect of dexamethasone (DEX), a specific agonist of glucocorticoid receptor (GR), on density and morphology of dendritic spines in adult male rat hippocampus by imaging of Lucifer Yellow-injected spines in slices. The application of 100 nM DEX (stressful high concentration) induced rapid modulation of the density and morphology of dendritic spines in CA1 pyramidal neurons within 1 h. The total spine density increased from 0.88 spines/mu m (control) to 1.36 spines/mu m (DEX-treated). DEX significantly increased the density of thin and mushroom type spines, however only a slight increase was observed for stubby and filopodium type spines. Because the presence of 10 mu M cycloheximide, an inhibitor of protein synthesis, did not suppress the DEX effect, these responses are probably non-genomic. Western immunoblot analysis demonstrated the localization of classical type GR in Triton-insoluble synaptosomal fractions (enriched in postsynaptic membranes) from hippocampal slices, suggesting a possible action site of DEX at spines. (c) 2005 Elsevier Inc. All rights reserved.