Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Survival / physiology
-
Cells, Cultured
-
Chemokine CX3CL1
-
Chemokines, CX3C / administration & dosage
-
Chemokines, CX3C / metabolism
-
Chemokines, CX3C / pharmacology
-
Chemokines, CX3C / physiology*
-
Drug Administration Schedule
-
Drug Combinations
-
Electric Conductivity
-
Excitatory Amino Acid Agonists / pharmacology
-
Glutamic Acid / pharmacology*
-
Hippocampus / drug effects*
-
Hippocampus / metabolism*
-
Hippocampus / physiology
-
Membrane Proteins / administration & dosage
-
Membrane Proteins / metabolism
-
Membrane Proteins / pharmacology
-
Membrane Proteins / physiology*
-
Neurons / drug effects
-
Neurons / metabolism
-
Neurons / physiology
-
Neuroprotective Agents* / administration & dosage
-
Neuroprotective Agents* / metabolism
-
Neuroprotective Agents* / pharmacology
-
Neurotoxins / pharmacology*
-
Rats
-
Rats, Wistar
-
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
-
Chemokine CX3CL1
-
Chemokines, CX3C
-
Cx3cl1 protein, rat
-
Drug Combinations
-
Excitatory Amino Acid Agonists
-
Membrane Proteins
-
Neuroprotective Agents
-
Neurotoxins
-
Glutamic Acid
-
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid