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首页> 外文期刊>The European Journal of Neuroscience >CNS region-specific regulation of glial glutamate transporter expression.
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CNS region-specific regulation of glial glutamate transporter expression.

机译：中枢神经系统区域特定调节胶质谷氨酸转运蛋白的表达。

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The neuronal cell death associated with certain neurodegenerative disorders as well as acute brain injuries is in part due to the reduced expression of glial glutamate transporters and the subsequent accumulation of toxic extracellular glutamate concentrations. Extracellular factors previously found to potently stimulate the expression of the glial glutamate transporters, GLT-1/EAAT2 and GLAST/EAAT1, in astroglial cultures of rat cerebral hemispheres are PACAP, TGF alpha, and EGF. In the present study, we sought to determine whether similar stimulatory influences apply for astroglia from other areas of the central nervous system (CNS). Immunoblot and real-time RT-PCR analysis of striatal astroglial cultures maintained for 72 h with PACAP, TGF alpha, or EGF revealed a prominent increase in GLT-1 and GLAST expression. In apparent contrast, all factors completely failed to affect GLT-1 and GLAST expression in astroglial cultures from the cerebellum, mesencephalon, and spinal cord between 36 h and 7 days. This failure was not due to the absence of functional recognition or transduction machineries for the extracellular factors as suggested by the additional observations that cerebellar, mesencephalic and spinal cord glia were capable of responding to stimulation with PACAP, TGF alpha, or EGF for 10 min with activation of CREB. Moreover, dibutyryl cyclic AMP (dbcAMP) potently promoted GLT-1 and/or GLAST expression in mesencephalic, cerebellar and spinal cord glia, further indicating that extracellular factors regulate glial glutamate transporter expression throughout the CNS. Together these findings identify PACAP, TGF alpha and EGF as potent regulators of glutamate transporter expression in striatal glia. In addition, these findings provide evidence for a CNS region-specific regulation of glial glutamate transport.
机译：与某些神经退行性疾病以及急性脑损伤相关的神经元细胞死亡部分归因于神经胶质谷氨酸转运蛋白的表达减少以及随后有毒的细胞外谷氨酸浓度的积累。先前发现在大鼠脑半球的星形胶质细胞培养物中，可有效刺激神经胶质谷氨酸转运蛋白GLT-1 / EAAT2和GLAST / EAAT1表达的细胞外因子为PACAP，TGFα和EGF。在本研究中，我们试图确定类似的刺激影响是否适用于中枢神经系统（CNS）其他区域的星形胶质细胞。用PACAP，TGFα或EGF维持72 h的纹状体星形胶质细胞培养物的免疫印迹和实时RT-PCR分析显示，GLT-1和GLAST表达显着增加。与之形成鲜明对比的是，在36小时至7天之间，所有因素完全无法影响小脑，中脑和脊髓的星形胶质细胞培养物中的GLT-1和GLAST表达。失败的原因不是由于缺乏对细胞外因子的功能识别或转导机制，正如其他观察结果所表明的那样，小脑，中脑和脊髓神经胶质细胞能够对PACAP，TGFα或EGF刺激10分钟。 CREB的激活。此外，二丁酰环AMP（dbcAMP）在中脑，小脑和脊髓神经胶质中有效地促进了GLT-1和/或GLAST的表达，进一步表明细胞外因子在整个CNS中调节神经胶质谷氨酸转运蛋白的表达。这些发现共同表明，PACAP，TGFα和EGF是纹状体胶质中谷氨酸转运蛋白表达的有效调节剂。此外，这些发现为中枢神经系统区域特异性调节胶质谷氨酸转运提供了证据。

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