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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS.
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Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS.

机译：启动子活性的变化揭示了在发育中的和成熟的中枢神经系统中神经胶质细胞谷氨酸转运蛋白的差异表达和生理学。

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Glutamate transporters regulate excitatory neurotransmission and prevent glutamate-mediated excitotoxicity in the CNS. To better study the cellular and temporal dynamics of the expression of these transporters, we generated bacterial artificial chromosome promoter Discosoma red [glutamate-aspartate transporter (GLAST)] and green fluorescent protein [glutamate transporter-1 (GLT-1)] reporter transgenic mice. Analysis of these mice revealed a differential activation of the transporter promoters not previously appreciated. GLT-1 promoter activity in the adult CNS is almost completely restricted to astrocytes, often and unexpectedly in a nonoverlapping pattern with GLAST. Spinal cord GLT-1 promoter reporter, protein density, and physiology were 10-fold lower than in brain, suggesting a possible mechanism for regional sensitivity seen in disease. The GLAST promoter is active in both radial glia and many astrocytes in the developing CNS but is downregulated in most astrocytes as the mice mature. In the adultCNS, the highest GLAST promoter activity was observed in radial glia, such as those located in the subgranular layer of the dentate gyrus. The continued expression of GLAST by these neural progenitors raises the possibility that GLAST may have an unanticipated role in regulating their behavior. In addition, GLAST promoter activation was observed in oligodendrocytes in white matter throughout many (e.g., spinal cord and corpus callosum), but not all (e.g., cerebellum), CNS fiber tracts. Overall, these studies of GLT-1 and GLAST promoter activity, protein expression, and glutamate uptake revealed a close correlation between transgenic reporter signals and uptake capacity, indicating that these mice provide the means to monitor the expression and regulation of glutamate transporters in situ.
机译：谷氨酸转运蛋白调节兴奋性神经传递并防止谷氨酸介导的CNS兴奋性毒性。为了更好地研究这些转运蛋白表达的细胞和时间动态，我们生成了细菌人工染色体启动子Discosoma红色[谷氨酸-天冬氨酸转运蛋白（GLAST）]和绿色荧光蛋白[谷氨酸转运蛋白-1（GLT-1）]报告基因转基因小鼠。对这些小鼠的分析揭示了先前未认识到的转运蛋白启动子的差异激活。在成年中枢神经系统中，GLT-1启动子活性几乎完全限于星形胶质细胞，通常与GLAST呈非重叠模式。脊髓GLT-1启动子报告基因，蛋白质密度和生理学比脑组织低10倍，这表明在疾病中发现区域敏感性的可能机制。 GLAST启动子在发育中的中枢神经系统的radial神经胶质细胞和许多星形胶质细胞中均具有活性，但随着小鼠的成熟，在大多数星形胶质细胞中均被下调。在成年CNS中，在放射状胶质细胞中观察到最高的GLAST启动子活性，例如位于齿状回的亚颗粒层中的那些。这些神经祖细胞持续表达GLAST的可能性增加了GLAST在调节其行为中可能具有意想不到的作用的可能性。另外，在许多（例如脊髓和fiber体）白质的少突胶质细胞中观察到了GLAST启动子的活化，但在所有（例如小脑）CNS纤维束中却观察不到。总的来说，对GLT-1和GLAST启动子活性，蛋白质表达和谷氨酸摄取的这些研究揭示了转基因报道信号与摄取能力之间的密切相关性，表明这些小鼠提供了监测谷氨酸转运蛋白原位表达和调控的手段。

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