Downregulation of glutamate transporters is associated with elevation in extracellular glutamate concentration following rat microsphere embolism
Downregulation of glutamate transporters is associated with elevation in extracellular glutamate concentration following rat microsphere embolism
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DOI：
10.1016/j.neulet.2007.11.021
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发表时间：
2008-01-17
影响因子：
2.5
通讯作者：
Fukunaga, Kohji
中科院分区：
文献类型：
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作者：
Han, Feng;Shioda, Norifumi;Fukunaga, Kohji
在星形胶质细胞和神经元中表达的钠依赖性谷氨酸转运体对于细胞外谷氨酸的清除是必不可少的。在本研究中，我们发现大鼠微球栓塞（ME）后，细胞外谷氨酸浓度升高与谷氨酸转运体的下调相关。微透析后立即观察到细胞外谷氨酸在大鼠纹状体的显着增加ME诱导，和谷氨酸仍然升高至少12小时后缺血。与此同时，损伤高氯化钾（146 mM）诱导的谷氨酸释放在纹状体72小时后ME。一致的持续增加细胞外谷氨酸，谷氨酸转运体EAAC 1和GLT-1的表达显着降低6小时后，没有变化的GLAST水平的侮辱。GLT-1表达在48小时内恢复到基础水平，而EAAC 1表达在ME后至少72小时仍然下降。GLT-1的恢复与星形胶质细胞标志物GFAP表达增加相关，而EACC 1水平显著降低与神经元标志物MAP 2水平降低相关，可能是由于脆弱神经元的丢失。两者合计，下调谷氨酸转运后ME与基础谷氨酸浓度和KCl诱导的谷氨酸释放在大脑中的失调。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Sodium-dependent glutamate transporters expressed in astroglial cells and neurons are essential for clearance of extracellular glutamate. In the present study, we found elevation of extracellular glutamate concentration associated with concomitant downregulation of glutamate transporters following rat microsphere embolism (ME). A marked increase in extracellular glutamate in the rat striatum was observed by microdialysis immediately after ME induction, and glutamate remained elevated at least 12 h after ischemia. Concomitantly, impairment of high KCI (146 mM)induced glutamate release was observed in the striatum 72 h after ME. Consistent with the persistent increase in extracellular glutamate, expression of the glutamate transporters EAAC1 and GLT-1 significantly decreased 6h after insult without a change in GLAST levels. GLT-1 expression was restored to basal levels within 48 h, whereas EAAC1 expression remained decreased up to at least 72 h after ME. Restoration of GLT-1 was associated with increased expression of the astroglial marker GFAP, whereas markedly reduced EACC1 levels were correlated with reduced levels of the neuronal marker MAP2, likely due to loss of vulnerable neurons. Taken together, downregulation of glutamate transporters after ME is associated with dysregulation of basal glutamate concentrations and KCl-induced glutamate release in the brain. (c) 2007 Elsevier Ireland Ltd. All rights reserved.