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

Myriam Catalano (1, 2) , Clotilde Lauro (2) , Raffaela Cipriani (2) , Giuseppina Chece (2) , Andrea Ponzetta (2) , Silvia Di Angelantonio (2, 3) , Davide Ragozzino (1, 2) , Cristina Limatola (1, 2)

1 NEUROMED I.R.C.C.S. - Istituto Neurologico Mediterraneo
2 Department of Physiology and Pharmacology
3 Center for Life Nano Science at Sapienza

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.

Domaines: Neurosciences [q-bio.NC]

Myriam Catalano, Clotilde Lauro, Raffaela Cipriani, Giuseppina Chece, Andrea Ponzetta, et al.. CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes.. Journal of Neuroimmunology, 2013, 263 (1-2), pp.75-82. ⟨10.1016/j.jneuroim.2013.07.020⟩. ⟨pasteur-01053833⟩