title: Fractalkine/CX3CL1 engages different neuroprotective responses upon selective glutamate receptor overactivation.
abstract: Neuronal death induced by overactivation of N-methyl-d-aspartate receptors (NMDARs) is implicated in the pathophysiology of many neurodegenerative diseases such as stroke, epilepsy and traumatic brain injury. This toxic effect is mainly mediated by NR2B-containing extrasynaptic NMDARs, while NR2A-containing synaptic NMDARs contribute to cell survival, suggesting the possibility of therapeutic approaches targeting specific receptor subunits. We report that fractalkine/CX3CL1 protects hippocampal neurons from NMDA-induced cell death with a mechanism requiring the adenosine receptors type 2A (A2AR). This is different from CX3CL1-induced protection from glutamate (Glu)-induced cell death, that fully depends on A1R and requires in part A3R. We show that CX3CL1 neuroprotection against NMDA excitotoxicity involves D-serine, a co-agonist of NR2A/NMDAR, resulting in cyclic AMP-dependent transcription factor cyclic-AMP response element-binding protein (CREB) phosphorylation.
authors: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome Rome, Italy.
authors: Clotilde
authors: C
authors: Lauro
authors: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome Rome, Italy ; Istituto di Ricovero e Cura a Carattere Scientifico NeuroMed Pozzilli, Italy.
authors: Myriam
authors: M
authors: Catalano
authors: Department of Biosciences, University of Milan Milan, Italy.
authors: Eleonora
authors: E
authors: Di Paolo
authors: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome Rome, Italy.
authors: Giuseppina
authors: G
authors: Chece
authors: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome Rome, Italy.
authors: Ida
authors: I
authors: de Costanzo
authors: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome Rome, Italy.
authors: Flavia
authors: F
authors: Trettel
authors: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome Rome, Italy ; Istituto di Ricovero e Cura a Carattere Scientifico NeuroMed Pozzilli, Italy.
authors: Cristina
authors: C
authors: Limatola
keywords: A2AR; CX3CL1; D-serine; NMDA; excitotoxicity; neuroprotection
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