title: CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes.
abstract: 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.
authors: 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. Electronic address: myriam.catalano@uniroma1.it.
authors: Myriam
authors: M
authors: Catalano
authors: Clotilde
authors: C
authors: Lauro
authors: Raffaela
authors: R
authors: Cipriani
authors: Giuseppina
authors: G
authors: Chece
authors: Andrea
authors: A
authors: Ponzetta
authors: Silvia
authors: S
authors: Di Angelantonio
authors: Davide
authors: D
authors: Ragozzino
authors: Cristina
authors: C
authors: Limatola
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000502:physiology*; D018920:Coculture Techniques; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005947:Glucose / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D027342:Excitatory Amino Acid Transporter 2; D018696:Neuroprotective Agents; C493395:Slc1a2 protein, rat; D005947:Glucose
keywords: A1R; Astrocytes; CX3CL1; GLT-1; Microglia; Neuroprotection