Altered expression of glutamate transporters in experimental autoimmune encephalomyelitis.
J Neuroimmunol
; 125(1-2): 170-8, 2002 Apr.
Article
em En
| MEDLINE
| ID: mdl-11960654
ABSTRACT
Amelioration of experimental autoimmune encephalomyelitis (EAE) by blockade of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), has been recently demonstrated [Nat. Med. 6 (2000) 67; Nat. Med. 6 (2000) 62]. However, the mechanisms underlying regulation of the extracellular glutamate concentration in EAE are unclear. To address this, we examined the expression of three distinct Na(+)-dependent glutamate transporters (GLT-1, GLAST and EAAC1) in the spinal cord of the Lewis rat EAE. EAE induced a dramatic increase in EAAC1 protein and mRNA levels, which corresponded closely with the course of neurological symptoms. In contrast, the levels of GLT-1 and GLAST protein were down-regulated in the spinal cord at the peak of disease symptoms, and no recovery was observed after remission. Furthermore, these changes in GLT-1, GLAST and EAAC1 expression were suppressed by treatment with NBQX. These results suggest that AMPA receptor activation precedes the altered expression of glutamate transporters, and that the dysregulation of extracellular glutamate concentration might play a critical role in pathological changes and neuronal dysfunction in EAE.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Medula Espinal
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Sistema X-AG de Transporte de Aminoácidos
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Simportadores
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Encefalomielite Autoimune Experimental
Limite:
Animals
Idioma:
En
Revista:
J Neuroimmunol
Ano de publicação:
2002
Tipo de documento:
Article