Glucocorticoid Regulation of GLT-1 Glutamate Transporter Isoform Expression in the Rat Hippocampus

Glucocorticoid Regulation of GLT-1 Glutamate Transporter Isoform Expression in the Rat Hippocampus
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DOI:
10.1159/000096092
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发表时间:
2006-01-01
期刊:
影响因子:
4.1
通讯作者:
Reagan, Lawrence P.
Reagan, Lawrence P.
中科院分区:
医学2区
文献类型:
--
作者:
Autry, Anita E.;Grillo, Claudia A.;Reagan, Lawrence P.

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背景:在大鼠海马中,主要的谷氨酸转运体是GLT-1及其最近鉴定的亚型GLT-1b。慢性束缚应激增加整个海马体的GLT-1b表达,同时更有选择性地增加CA 3区域的GLT-1表达。这些研究表明,GLT-1b的表达是调节应激水平的糖皮质激素(GC)和GLT-1的表达是调节应激诱导的细胞外谷氨酸水平在CA 3区的增加。研究方法:为了区分GC和谷氨酸的作用,我们研究了GLT-1亚型表达肾上腺切除(ADX)大鼠和大鼠暴露于应激水平的GC。结果如下:与假手术对照组或给予GC替代的ADX大鼠相比,ADX大鼠GLT-1b mRNA或蛋白水平无显著差异。然而,大鼠暴露于应激水平的GC表现出增加GLT-1b蛋白表达的CA 3区和齿状回。GLT-1 mRNA的表达增加ADX,增加GC替代抑制。类似地,GC的应激水平增加了整个海马的GLT-1蛋白表达。结论:综上所述,这些数据表明,GLT-1b蛋白的表达是由GC的应激水平,而GLT-1 mRNA和蛋白表达的调节提供了GC在中枢神经系统中的双相作用的另一个例子。版权所有(C)2006 S. Karger AG,巴塞尔
Background: In the rat hippocampus, the predominate glutamate transporters are GLT-1 and its recently identified isoform, GLT-1b. Chronic restraint stress increases GLT-1b expression throughout the hippocampus while more selectively increasing GLT-1 expression in the CA3 region. These studies suggest that GLT-1b expression is regulated by stress levels of glucocorticoids (GCs) and GLT-1 expression is regulated by stress-induced increases in extracellular glutamate levels in the CA3 region. Methods: In order to differentiate between the actions of GCs and glutamate, we examined GLT-1 isoform expression in adrenalectomized (ADX) rats and rats exposed to stress levels of GCs. Results: ADX rats revealed no significant differences in GLT-1b mRNA or protein levels compared to sham-operated controls or ADX rats given GC replacement. However, rats exposed to stress levels of GCs exhibited increases in GLT-1b protein expression in the CA3 region and the dentate gyrus. GLT-1 mRNA expression was increased by ADX, increases that were inhibited by GC replacement. Similarly, stress levels of GCs increased GLT-1 protein expression throughout the hippocampus. Conclusions: Taken together, these data indicate that GLT-1b protein expression is regulated by stress levels of GCs while the regulation of GLT-1 mRNA and protein expression provides another example of the biphasic actions of GCs in the central nervous system. Copyright (C) 2006 S. Karger AG, Basel