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GluR2‐free α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate receptors intensify demyelination in experimental autoimmune encephalomyelitis
Author(s) -
Bannerman Peter,
Horiuchi Makoto,
Feldman Daniel,
Hahn Ashleigh,
Itoh Aki,
See Jill,
Jia Zheng Ping,
Itoh Takayuki,
Pleasure David
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04612.x
Subject(s) - ampa receptor , experimental autoimmune encephalomyelitis , excitotoxicity , myelin oligodendrocyte glycoprotein , multiple sclerosis , encephalomyelitis , receptor , neuroscience , glutamate receptor , myelin basic protein , immunology , biology , myelin , central nervous system , genetics
We adopted a genetic approach to test the importance of edited GluR2‐free, Ca 2+ ‐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 Ca 2+ ‐permeable AMPA receptors would be therapeutic in multiple sclerosis.