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谷氨酸转运体1和谷氨酸天冬氨酸转运体在蒙古沙鼠短暂性脑缺血模型中的表达

The Expression of GLAST and GLT1 in a Transient Cerebral Ischemia Mongolian Gerbil Model.

作者信息

Shen Yanling, Lu Huiling, Xu Runnan, Tian Haibo, Xia Xuewei, Zhou Fiona H, Wang Liping, Dong Jianghui, Sun Liyuan

机构信息

Department of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, Guangxi 541004, People's Republic of China.

Department of Pathology, Affiliated Chenggong Hospital, Xiamen University, Xiamen, Fujian 361000, People's Republic of China.

出版信息

Neuropsychiatr Dis Treat. 2020 Mar 23;16:789-800. doi: 10.2147/NDT.S238455. eCollection 2020.

Abstract

PURPOSE

Excitatory amino acid transporters (EAATs) have an indispensable function in the reuptake of extracellular glutamate. To investigate the relationship and the expression of neuronal and astrocytic markers after brain ischemia, the temporal profile of glial EAATs in both peripheral and core regions of the cortex was examined.

METHODS

Transient common carotid artery occlusion was used to induce unilateral transient forebrain ischemia of Mongolian gerbils, and post-ischemic brains (6 h to 2 w) were collected and prepared for immunohistochemical and Western blotting analysis of glutamine synthetase (GS), GLT-1, GLAST, S100β, and NeuN, and for Alizarin red staining of calcium deposits.

RESULTS

The expression of GLAST and GLT-1 were significantly escalated at 6 h both in the core and periphery regions, while reduced from 12 h to 2 w in the core region post-ischemia. GS-positive cells increased at 6 h both in the core and periphery regions, while the density of Alizarin red-positive cells increased and peaked at 12 h in the ischemic cortex. The density of S100β-positive cells decreased in the ischemic core and increased in the periphery region. Immunofluorescence staining showed that S100β and TUNEL double-positive cells increased at 12 h in the core region.

CONCLUSION

The results of GLT-1 and GLAST expression in the cortex indicate that their up-regulation was time-dependent and occurred in the acute post-ischemia period, whereas their down-regulation was region-dependent and it is involved in the pathological progress of nerve cell and glial cell death, and has a series of cascade reactions.

摘要

目的

兴奋性氨基酸转运体(EAATs)在细胞外谷氨酸的重摄取中发挥着不可或缺的作用。为了研究脑缺血后神经元和星形胶质细胞标志物的关系及表达情况,我们检测了皮质外周和核心区域胶质EAATs的时间变化情况。

方法

采用短暂性双侧颈总动脉闭塞法诱导蒙古沙鼠单侧短暂性前脑缺血,收集缺血后6小时至2周的脑组织,用于谷氨酰胺合成酶(GS)、谷氨酸转运体1(GLT-1)、谷氨酸-天冬氨酸转运体(GLAST)、S100β蛋白和神经元核抗原(NeuN)的免疫组织化学和蛋白质印迹分析,以及钙沉积的茜素红染色。

结果

缺血6小时时,核心区和外周区GLAST和GLT-1的表达均显著升高,而缺血后12小时至2周核心区的表达降低。GS阳性细胞在缺血6小时时核心区和外周区均增加,而缺血皮质中茜素红阳性细胞密度在12小时时增加并达到峰值。缺血核心区S100β阳性细胞密度降低,外周区增加。免疫荧光染色显示,缺血核心区12小时时S100β和TUNEL双阳性细胞增加。

结论

皮质中GLT-1和GLAST的表达结果表明,它们的上调具有时间依赖性,发生在缺血后急性期,而下调具有区域依赖性,参与神经细胞和胶质细胞死亡的病理进程,并引发一系列级联反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9a6/7125407/56f0c64a9671/NDT-16-789-g0001.jpg

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