Cortical death caused by striatal administration of AMPA and interleukin-1 is mediated by activation of cortical NMDA receptors.
Striatal coadministration of interleukin-1beta (IL-1beta) with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA) in rats results in widespread cortical cell death not caused by either treatment alone. This cortical damage was unaffected by cortical infusion of the AMPA-receptor antagonist NBQX. Cortical infusion of an NMDA-receptor antagonist D-AP5 significantly inhibited (57%; P < 0.05) cortical death, but had no effect on the local striatal death. Thus, cortical neuronal death induced by striatal S-AMPA and human recombinant interleukin-1beta (hrIL-1beta) is mediated by activation of NMDA receptors in the cortex. The authors propose that IL-1beta actions on AMPA-receptor mediated cell death may involve the activation of polysynaptic pathways from the striatum to the cortex.
Allan
S M
SM
School of Biological Sciences, University of Manchester, UK.
Rothwell
N J
NJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007375:Interleukin-1; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid