Role of P2X7 receptors in ischemic and excitotoxic brain injury in vivo.
Purinergic P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1beta (IL-1beta), a key mediator in neurodegeneration. The authors tested the hypothesis that ATP, acting at P2X7 receptors, contributes to experimentally induced neuronal death in rodents in vivo. Deletion of P2X7 receptors (P2X7 knockout mice) did not affect cell death induced by temporary cerebral ischemia, which was reduced by treatment with IL-1 receptor antagonist (IL-1RA). Treatment of mice with P2X7 antagonists did not affect ischemic or excitotoxic cell death, suggesting that P2X7 receptors are not primary mediators of experimentally induced neuronal death.
Le Feuvre
Rosalind A
RA
School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK. mqbssral@man.ac.uk
Brough
David
D
Touzani
Omar
O
Rothwell
Nancy J
NJ
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000503:physiopathology*; D016923:Cell Death / Q000187:drug effects; D005971:Glutamates / Q000737:chemistry; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D009474:Neurons / Q000502:physiology; D009498:Neurotoxins; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D012795:Sialoglycoproteins / Q000494:pharmacology; D013237:Stereoisomerism
D005971:Glutamates; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D009498:Neurotoxins; C546469:P2rx7 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D012795:Sialoglycoproteins; C066302:2,4-methanoglutamate