GluR2-free α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors intensify demyelination in experimental autoimmune encephalomyelitis

Peter Bannerman, Makoto Horiuchi, Daniel Feldman, Ashleigh Hahn, Aki Itoh, Jill See, Zheng Ping Jia, Takayuki Ito, David E Pleasure

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


We adopted a genetic approach to test the importance of edited GluR2-free, Ca2+-permeable, α-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA) receptors in the pathophysiology of experimental autoimmune encephalomyelitis, an inflammatory demyelinative disorder resembling multiple sclerosis. Initial studies showed that oligodendroglial lineage cells from mice lacking functional copies of the gene encoding the GluR3 AMPA receptor subunit (Gria3) had a diminished capacity to assemble edited GluR2-free AMPA receptors, and were resistant to excitotoxicity in vitro. Neurological deficits and spinal cord demyelination elicited by immunization with myelin oligodendrocyte glycoprotein peptide were substantially milder in these Gria3 mutant mice than in their wild-type littermates. These results support the hypothesis that oligodendroglial excitotoxicity mediated by AMPA receptors that do not contain edited GluR2 subunits contributes to demyelination in experimental autoimmune encephalomyelitis, and suggest that inhibiting these Ca2+-permeable AMPA receptors would be therapeutic in multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)1064-1070
Number of pages7
JournalJournal of Neurochemistry
Issue number4
StatePublished - Aug 2007


  • Excitotoxicity
  • Experimental autoimmune encephalomyelitis
  • Glutamate receptor
  • Oligodendroglia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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