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 fractalkine/CX3CL1 on survival of hippocampal neurons exposed to excitotoxic doses of Glu. We found that: CX3CL1 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; CX3CL1 reduces the Glu-activated whole-cell current through mechanisms dependent on intracellular Ca2+; CX3CL1 is released from hippocampal cells after excitotoxic insult, likely providing an endogenous protective mechanism against excitotoxic cell death.
Limatola
Cristina
C
Istituto Pasteur-Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza BEMM, Università di Roma La Sapienza, P.le A. Moro 5, I00185 Rome, Italy. cristina.limatola@uniroma1.it
Lauro
Clotilde
C
Catalano
Myriam
M
Ciotti
Maria Teresa
MT
Bertollini
Cristina
C
Di Angelantonio
Silvia
S
Ragozzino
Davide
D
Eusebi
Fabrizio
F
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004553:Electric Conductivity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D004338:Drug Combinations; D018690:Excitatory Amino Acid Agonists; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid