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

Takeshi Takarada, Tomoya Hara, Shiho Konishi, Ryota Nakazato, Yukio Yoneda

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 Ca 2+ 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.

Original languageEnglish
Pages (from-to)187-194
Number of pages8
JournalJapanese Journal of Neuropsychopharmacology
Volume31
Issue number4
Publication statusPublished - Aug 2011
Externally publishedYes

Fingerprint

D-Aspartic Acid
Middle Cerebral Artery Infarction
Cerebrum
N-Methyl-D-Aspartate Receptors
Down-Regulation
Reperfusion
Ionotropic Glutamate Receptors
Messenger RNA
Microtubule-Associated Proteins
Protein Subunits
Brain
Glutamic Acid
Proteins
Cell Death
aspartic acid receptor

Keywords

  • Ischemic cytotoxicity
  • Microglia
  • Neurons
  • NMDA receptor

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology
  • Pharmacology (medical)
  • Pharmacology

Cite this

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. / Takarada, Takeshi; Hara, Tomoya; Konishi, Shiho; Nakazato, Ryota; Yoneda, Yukio.

In: Japanese Journal of Neuropsychopharmacology, Vol. 31, No. 4, 08.2011, p. 187-194.

Research output: Contribution to journalArticle

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