CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes
CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes
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DOI：
10.1016/j.jneuroim.2013.07.020
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发表时间：
2013-10-15
影响因子：
3.3
通讯作者：
Limatola, Cristina
中科院分区：
文献类型：
--
作者：
Catalano, Myriam;Lauro, Clotilde;Limatola, Cristina
在本文中，我们首次表明：i) CX3CL1 对抗兴奋性毒性的神经保护活性需要星形胶质细胞； ii) 抑制谷氨酸转运蛋白 1 (GLT-1) 会损害 CX3CL1 介导的神经保护作用； iii) CX3CL1 增加星形胶质细胞上的 GLT-1 活性。 CX3CL1 对星形胶质细胞诱导的 GLT-1 活性的调节需要 A1 腺苷受体 (A(1)R) 的存在和活性，该受体被特异性拮抗剂 DPCPX 阻断，并且在 A(1)R(-/-) 星形胶质细胞中不存在。这些数据介绍了星形胶质细胞作为 CX3CL1 介导的小胶质细胞和神经元之间信号传导的活跃参与者，确定 GLT-1 是 CX3CL1 神经保护活性的关键介质。 (C) 2013 Elsevier B.V. 保留所有权利。
In this paper we show for the first time that: i) astrocytes are required for the neuroprotective activity of CX3CL1 against excitotoxicity; ii) inhibition of the glutamate transporter 1 (GLT-1) prejudices CX3CL1-mediated neuroprotection; iii) CX3CL1 increases GLT-1 activity on astrocytes. The modulation of GLT-1 activity induced by CX3CL1 on astrocytes requires the presence and the activity of A1 adenosine receptor (A(1)R), being blocked by the specific antagonist DPCPX and absent in A(1)R(-/-) astrocytes. These data introduce the astrocytes as active players in CX3CL1-mediated signaling between microglia and neurons, identifying GLT-1 as a key mediator of the neuroprotective activity of CX3CL1. (C) 2013 Elsevier B.V. All rights reserved.