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 journalArticle

14 Citations (Scopus)

Abstract

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
Volume102
Issue number4
DOIs
StatePublished - Aug 2007

Fingerprint

AMPA Receptors
Autoimmune Experimental Encephalomyelitis
Demyelinating Diseases
Multiple Sclerosis
Myelin-Oligodendrocyte Glycoprotein
Immunization
Gene encoding
Spinal Cord
Peptides
Genes
Therapeutics

Keywords

  • Excitotoxicity
  • Experimental autoimmune encephalomyelitis
  • Glutamate receptor
  • Oligodendroglia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

GluR2-free α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors intensify demyelination in experimental autoimmune encephalomyelitis. / Bannerman, Peter; Horiuchi, Makoto; Feldman, Daniel; Hahn, Ashleigh; Itoh, Aki; See, Jill; Jia, Zheng Ping; Ito, Takayuki; Pleasure, David E.

In: Journal of Neurochemistry, Vol. 102, No. 4, 08.2007, p. 1064-1070.

Research output: Contribution to journalArticle

Bannerman, Peter ; Horiuchi, Makoto ; Feldman, Daniel ; Hahn, Ashleigh ; Itoh, Aki ; See, Jill ; Jia, Zheng Ping ; Ito, Takayuki ; Pleasure, David E. / GluR2-free α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors intensify demyelination in experimental autoimmune encephalomyelitis. In: Journal of Neurochemistry. 2007 ; Vol. 102, No. 4. pp. 1064-1070.
@article{f3c36064d513465cbc3412b7c7801a55,
title = "GluR2-free α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors intensify demyelination in experimental autoimmune encephalomyelitis",
abstract = "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.",
keywords = "Excitotoxicity, Experimental autoimmune encephalomyelitis, Glutamate receptor, Oligodendroglia",
author = "Peter Bannerman and Makoto Horiuchi and Daniel Feldman and Ashleigh Hahn and Aki Itoh and Jill See and Jia, {Zheng Ping} and Takayuki Ito and Pleasure, {David E}",
year = "2007",
month = "8",
doi = "10.1111/j.1471-4159.2007.04612.x",
language = "English (US)",
volume = "102",
pages = "1064--1070",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - GluR2-free α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors intensify demyelination in experimental autoimmune encephalomyelitis

AU - Bannerman, Peter

AU - Horiuchi, Makoto

AU - Feldman, Daniel

AU - Hahn, Ashleigh

AU - Itoh, Aki

AU - See, Jill

AU - Jia, Zheng Ping

AU - Ito, Takayuki

AU - Pleasure, David E

PY - 2007/8

Y1 - 2007/8

N2 - 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.

AB - 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.

KW - Excitotoxicity

KW - Experimental autoimmune encephalomyelitis

KW - Glutamate receptor

KW - Oligodendroglia

UR - http://www.scopus.com/inward/record.url?scp=34547461178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547461178&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2007.04612.x

DO - 10.1111/j.1471-4159.2007.04612.x

M3 - Article

C2 - 17472701

AN - SCOPUS:34547461178

VL - 102

SP - 1064

EP - 1070

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -