Type-2 astrocyte-like cells are more resistant than oligodendrocyte-like cells against non-N-methyl-D-aspartate glutamate receptor-mediated excitotoxicity

Yoko Yamaya, Akira Yoshioka, Shinji Saiki, Natsuko Yuki, Genjiro Hirose, David E Pleasure

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Glutamate causes excitotoxicity via non-N-methyl-D-aspartate (NMDA) glutamate receptors (GluR) in oligodendrocytes. Because both oligodendrocytes and type 2 astrocytes are differentiated from oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells, we investigated whether astrocytes are also vulnerable to non-NMDA GluR-mediated excitotoxicity. For these studies, oligodendrocyte-like cells (OLC) and type 2 astrocyte-like cells (2ALC) were derived from CG-4 cells, an immortalized rat O-2A progenitor cell line. About 50% of 2ALC were positive for glial fibrillary acidic protein and 90% were positive for A2B5, verifying that these cells have an type 2 astrocytic phenotype. A 24-hr exposure of OLC to 2 mM kainate, an activator of non-NMDA GluR, caused cell damage as shown by the release of lactate dehydrogenase. The extent of kainate-induced OLC damage was increased by cyclothiazide. In contrast, exposure of 2ALC to 2 mM kainate alone did not induce injury, though mild 2ALC injury was elicited by exposure to 2 mM kainate plus 100 μM cyclothiazide. Furthermore, we found that the kainate induced Ca2+ uptake by 2ALC was 27.5% of that induced by kainate in OLC. Finally, both OLC and 2ALC expressed non-NMDA GluR subunit mRNAs, including GluR2, GluR3, GluR4, GluR6, GluR7, KA1, and KA2, but quantitative Western blot analysis revealed higher immunodetectable GluR2 and lower immunodetectable GluR3 and GluR4 in 2ALC than in OLC. Together, these results suggest that astrocytes are relatively resistant to non-NMDA GluR-mediated excitotoxicity because they have a higher expression of GluR2 and lower expression of GluR3 and GluR4.

Original languageEnglish (US)
Pages (from-to)588-598
Number of pages11
JournalJournal of Neuroscience Research
Volume70
Issue number4
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

Keywords

  • Astrocytes
  • Ca uptake
  • Excitotoxicity
  • Non-N-methyl-D-aspartate glutamate receptors
  • Oligodendrocytes

ASJC Scopus subject areas

  • Neuroscience(all)

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