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

Autor: Takayuki Itoh, Daniel H. Feldman, Ashleigh Hahn, Makoto Horiuchi, David E Pleasure, Jill See, Peter Bannerman, Aki Itoh, Zheng Ping Jia
Rok vydání: 2007
Předmět:
medicine.medical_specialty
Kainic acid
Encephalomyelitis
Autoimmune
Experimental
Patch-Clamp Techniques
Encephalomyelitis
Excitotoxicity
AMPA receptor
Biology
medicine.disease_cause
Biochemistry
Statistics
Nonparametric
Myelin oligodendrocyte glycoprotein
Membrane Potentials
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Myelin
Mice
Internal medicine
medicine
Animals
Excitatory Amino Acid Agents
RNA
Messenger
Receptors
AMPA
Cells
Cultured
Mice
Knockout
Kainic Acid
Reverse Transcriptase Polymerase Chain Reaction
Experimental autoimmune encephalomyelitis
Glutamate receptor
Brain
medicine.disease
Molecular biology
Endocrinology
medicine.anatomical_structure
nervous system
chemistry
Animals
Newborn
Gene Expression Regulation
Receptors
Glutamate
biology.protein
Female
Spermine
Neuroglia
Demyelinating Diseases
Zdroj: Journal of neurochemistry. 102(4)
ISSN: 0022-3042
Popis: We adopted a genetic approach to test the importance of edited GluR2-free, Ca(2+)-permeable, alpha-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.
Databáze: OpenAIRE
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