AUTHOR=Lauro Clotilde , Catalano Myriam , Di Paolo Eleonora , Chece Giuseppina , de Costanzo Ida , Trettel Flavia , Limatola Cristina 

TITLE=Fractalkine/CX3CL1 engages different neuroprotective responses upon selective glutamate receptor overactivation

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=8

YEAR=2015

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2014.00472

DOI=10.3389/fncel.2014.00472

ISSN=1662-5102

ABSTRACT=<p>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 2<sub>A</sub> (A<sub>2A</sub>R). This is different from CX3CL1-induced protection from glutamate (Glu)-induced cell death, that fully depends on A<sub>1</sub>R and requires in part A<sub>3</sub>R. 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.</p>