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. © 2013 Elsevier B.V.
CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes / Catalano, Myriam; Lauro, Clotilde; Cipriani, Raffaela; Chece, Giuseppina; Ponzetta, Andrea; DI ANGELANTONIO, Silvia; Ragozzino, Davide Antonio; Limatola, Cristina. - In: JOURNAL OF NEUROIMMUNOLOGY. - ISSN 0165-5728. - STAMPA. - 263:1-2(2013), pp. 75-82. [10.1016/j.jneuroim.2013.07.020]