CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes

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• 作者：Myriam Catalano ; Clotilde Lauro ; Raffaela Cipriani ; Giuseppina Chece ; Andrea Ponzetta ; Silvia Di Angelantonio ; Davide Ragozzino ; Cristina Limatola
• 关键词：CX3CL1 ; Neuroprotection ; GLT-1 ; Astrocytes ; Microglia ; A1R
• 刊名：Journal of Neuroimmunology
• 出版年：2013
• 出版时间：15 October, 2013
• 年：2013
• 卷：263
• 期：1-2
• 页码：75-82
• 全文大小：700 K

文摘

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.