title: Selective downregulation of N-methyl-D-aspartate receptor (NMDAR) rather than non-NMDAR subunits in ipsilateral cerebral hemispheres in rats with middle cerebral artery occlusion.
abstract: Ischemic brain damage is believed to involve the drastic increase in extracellular glutamate levels after reperfusion and subsequent overactivation of both N-methyl-D-aspartate (NMDA) receptor (NMDAR) and non-NMDAR channels for delayed neuronal cell death mediated by Ca2+ overload. In this study, we evaluated expression profiles of mRNA and corresponding proteins for different subunits of NMDAR and non-NMDAR in brains of rats with transient middle cerebral artery occlusion (MCAO). Cellular vitality was markedly reduced in proportion to increasing durations of MCAO for 1 to 8 h when determined 1 day after reperfusion. Within 7 days after reperfusion, MCAO for 2 h led to a gradual decrease in the neuronal marker microtubules-associated protein-2 (MAP2) level in the ipsilateral cerebral hemisphere, in addition to inducing a transient increase in the microglial marker CD11b expression without affecting the astroglial marker protein levels. MCAO for 2 h significantly decreased the expression of both mRNA and corresponding proteins for NR1, NR2A and NR2B subunits of NMDAR, but not for non-NMDAR subunits, in the ipsilateral hemisphere. These results suggest that NMDAR may be preferentially down-regulated in response to ischemic signal inputs amongst three different subtypes of ionotropic glutamate receptors in rats with MCAO.
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takarada
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hara
authors.forename: Shiho
authors.initials: S
authors.lastname: Konishi
authors.forename: Ryota
authors.initials: R
authors.lastname: Nakazato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D054022:Cerebrum / Q000378:metabolism*; D015536:Down-Regulation; D018698:Glutamic Acid / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D002118:Calcium