Fondazione Cenci Bolognetti, Department of Physiology and Pharmacology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; IRCCS Neuromed, Via Atinese 18, 86077 Pozzilli, Italy.
J Neuroimmunol. 2013 Oct 15;263(1-2):75-82. doi: 10.1016/j.jneuroim.2013.07.020. Epub 2013 Aug 8.
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 (A1R), being blocked by the specific antagonist DPCPX and absent in A1R(-/-) 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.
在本文中，我们首次表明：i）星形胶质细胞是 CX3CL1 对抗兴奋毒性的神经保护活性所必需的；ii）谷氨酸转运蛋白 1（GLT-1）的抑制会损害 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 对星形胶质细胞的 GLT-1 活性的调节需要 A1 腺苷受体（A1R）的存在和活性，其被特异性拮抗剂 DPCPX 阻断，并且在 A1R（-/-）星形胶质细胞中不存在。这些数据将星形胶质细胞引入到 CX3CL1 介导的小胶质细胞和神经元之间的信号转导中作为活跃的参与者，确定 GLT-1 是 CX3CL1 的神经保护活性的关键介质。
