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Selective up-regulation of GLT-1 in cultured astrocytes exposed to soluble mediators released by activated microglia.

机译:暴露于活化小胶质细胞释放的可溶性介体的培养星形胶质细胞中GLT-1的选择性上调。

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摘要

Impaired glial glutamate uptake is commonly involved in neuronal damages observed in acute and chronic nervous disorders. As nervous insults are frequently associated with local inflammation involving microglia, this study aims at exploring the link between activated microglia and altered glutamate uptake in astrocytes. The regulation of the expression and activity of type 1 glutamate transporter (GLT-1) was examined after exposing cultures of rat astrocytes to conditioned medium from lipopolysaccharide-activated microglia cultures. Significant increases in GLT-1 mRNA expression and dihydrokainate sensitive uptake of aspartate were observed after 72h of treatment. These effects were reproduced by direct exposure of the astrocyte cultures to tumor necrosis factor alpha, a major cytokine released by activated microglia. The regulation of GLT-1 activity in response to inflammatory stimuli was also evidenced in cells exposed to dibutyryl cAMP, recognised as a model of reactive astrocytes in which the expression of this glutamate transporter is constitutively enhanced. Taken together, these results suggest that the GLT-1-dependent control of glutamate neurotransmission by either naive or chemically activated astrocytes is influenced by microglia-mediated inflammation.
机译:在急性和慢性神经疾病中观察到神经胶质谷氨酸摄取受损通常与神经元损伤有关。由于神经损伤常常与涉及小胶质细胞的局部炎症有关,因此本研究旨在探讨活化的小胶质细胞与星形胶质细胞谷氨酸吸收改变之间的联系。将大鼠星形胶质细胞培养物暴露于脂多糖激活的小胶质细胞培养物的条件培养基中后,检查了1型谷氨酸转运蛋白(GLT-1)的表达和活性的调节。处理72小时后,观察到GLT-1 mRNA表达的显着增加和天冬氨酸对二氢海藻酸酯的吸收。通过星形胶质细胞培养物直接暴露于肿瘤坏死因子α(活化的小胶质细胞释放的主要细胞因子)来再现这些效应。在暴露于二丁酰cAMP的细胞中也证实了GLT-1活性对炎症刺激的调节,该细胞被认为是反应性星形胶质细胞的模型,其中该谷氨酸转运蛋白的表达在组成上得到增强。两者合计,这些结果表明天真或化学激活的星形胶质细胞对谷氨酸神经传递的GLT-1依赖性控制受到小胶质细胞介导的炎症的影响。

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