Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity

Excitotoxicity is a cell death caused by excessive exposure to glutamate (Glu), contributing to neuronal degeneration in many acute and chronic CNS diseases. We explored the role of fractalkin/CX(3)CL1 on survival of hippocampal neurons exposed to excitotoxic doses of Glu. We found that: CX(3)CL1 reduces excitotoxicity when co-applied with Glu, through the activation of the ERK1/2 and PI3K/Akt pathways, or administered up to 8 h after Glu insult; CX(3)CL1 reduces the Glu-activated whole-cell current through mechanisms dependent on intracellular Ca2+; CX(3)CL1 is released from hippocampal cells after excitotoxic insult, likely providing an endogenous protective mechanism against excitotoxic cell death. (C) 2005 Elsevier B.V. All rights reserved.