Spatial and temporal changes in promoter activity of the astrocyte glutamate transporter GLT1 following traumatic spinal cord injury.
Spatial and temporal changes in promoter activity of the astrocyte glutamate transporter GLT1 following traumatic spinal cord injury.
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DOI：
10.1002/jnr.22624
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发表时间：
2011-07
影响因子：
4.2
通讯作者：
Maragakis, Nicholas J.
中科院分区：
文献类型：
--
作者：
Lepore, Angelo C.;O'Donnell, John;Bonner, Joseph F.;Paul, Courtney;Miller, Mark E.;Rauck, Britta;Kushner, Robert A.;Rothstein, Jeffrey D.;Fischer, Itzhak;Maragakis, Nicholas J.
创伤性脊髓损伤（SCI）后，有机会通过减少继发性细胞丢失来保护功能。星形胶质细胞在成年CNS中起着至关重要的作用，并负责绝大多数谷氨酸缓冲，可能防止神经元和少突胶质细胞的兴奋性毒性损失。我们使用转基因BAC-GLT 1-eGFP启动子报告小鼠研究了中度胸挫伤SCI后主要星形胶质细胞谷氨酸转运蛋白GLT 1基因表达的时空变化。在背柱白色物质中，SCI后每个区域的GLT 1-eGFP表达的总强度在损伤中心以及没有组织损失发生的喙部和尾部区域显著降低。GLT 1表达的这种区域性降低是由于GLT 1-eGFP+细胞的显著损失，部分原因是白色和灰质中eGFP+/GFAP+星形胶质细胞的凋亡。损伤后，多个灰质区域中表达GLT 1-eGFP的细胞数量也减少;然而，由于星形胶质细胞继续表达GLT 1-eGFP，灰质中的区域GLT 1-eGFP表达持续甚至增加。尽管SCI后损伤部位和周围完整脊髓中GFAP+细胞数量增加，但大多数增殖的Ki 67 +/GFAP+星形胶质细胞不表达GLT 1-eGFP。这些研究结果表明，空间和时间的变化，GLT 1表达后观察到的SCI结果从星形胶质细胞死亡和基因表达的变化，在存活的星形胶质细胞。结果还表明，SCI后，星形胶质细胞的一个显着的部分缺乏GLT 1的表达，可能损害谷氨酸稳态星形胶质细胞的重要作用。
After traumatic spinal cord injury (SCI), there is an opportunity for preserving function by attenuating secondary cell loss. Astrocytes play crucial roles in the adult CNS and are responsible for the vast majority of glutamate buffering, potentially preventing excitotoxic loss of neurons and oligodendrocytes. We examined spatial and temporal changes in gene expression of the major astrocyte glutamate transporter GLT1 following moderate thoracic contusion SCI using transgenic BAC-GLT1-eGFP promoter reporter mice. In dorsal column white matter, total intensity of GLT1-eGFP expression per region was significantly reduced following SCI at both lesion epicenter and at rostral and caudal areas where no tissue loss occurred. This regional decrease in GLT1 expression was due to significant loss of GLT1-eGFP+ cells, partially accounted for by apoptosis of eGFP+/GFAP+ astrocytes in both white and gray matter. There were also decreased numbers of GLT1-eGFP-expressing cells in multiple gray matter regions following injury; nevertheless, there was sustained or even increased regional GLT1-eGFP expression in gray matter as a result of up-regulation in astrocytes that continued to express GLT1-eGFP. Although there were increased numbers of GFAP+ cells both at the lesion site and in surrounding intact spinal cord following SCI, the majority of proliferating Ki67+/GFAP+ astrocytes did not express GLT1-eGFP. These findings demonstrate that spatial and temporal alterations in GLT1 expression observed after SCI result from both astrocyte death and gene expression changes in surviving astrocytes. Results also suggest that following SCI a significant portion of astrocytes lacks GLT1 expression, possibly compromising the important role of astrocytes in glutamate homeostasis.
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