title: Sublethal oxygen-glucose deprivation alters hippocampal neuronal AMPA receptor expression and vulnerability to kainate-induced death.
abstract: Recent studies have suggested that rats subjected to transient global brain ischemia develop depressed expression of GluR-B in CA1 hippocampal neurons. The present study was performed to determine whether a similar change in AMPA receptor expression could be triggered in vitro by sublethal oxygen-glucose deprivation in rat hippocampal neuronal cultures. mRNA was extracted from individual hippocampal neurons via patch electrodes and amplified by RT-PCR 24-48 hr after sublethal oxygen-glucose deprivation. Compared with controls, insulted neurons expressed increased levels of GluR-D flop. As an indication that this change in receptor expression was functionally significant, insulted cultures exhibited increased AMPA- or kainate-induced 45Ca2+ accumulation sensitive to Joro spider toxin and increased vulnerability to kainate-induced death. These data support the hypothesis that exposure to ischemia may enhance subsequent hippocampal neuronal vulnerability to AMPA receptor-mediated excitotoxicity by modifying the relative expression of AMPA receptor subunits in a manner that promotes Ca2+ permeability.
authors.affiliation: Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Ying
authors.forename: J H
authors.initials: JH
authors.lastname: Weishaupt
authors.forename: M
authors.initials: M
authors.lastname: Grabb
authors.forename: L M
authors.initials: LM
authors.lastname: Canzoniero
authors.forename: S L
authors.initials: SL
authors.lastname: Sensi
authors.forename: C T
authors.initials: CT
authors.lastname: Sheline
authors.forename: H
authors.initials: H
authors.lastname: Monyer
authors.forename: D W
authors.initials: DW
authors.lastname: Choi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D019194:Ischemic Preconditioning; D007608:Kainic Acid / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000737:chemistry* / Q000166:cytology* / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000235:genetics*; D013111:Spider Venoms / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C044936:JSTX spider toxin; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D011810:Quinoxalines; D012333:RNA, Messenger; D018091:Receptors, AMPA; D013111:Spider Venoms; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005947:Glucose; D007608:Kainic Acid; D002118:Calcium