Efeitos da administração intraestriatal aguda de ácido quinolítico sobre o citoesqueleto de células neurais de ratos

AUTOR(ES)

Paula Pierozan

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

2010

RESUMO

In the present study we investigated the effect of in vivo intrastriatal injection of quinolinic acid (QA) on rat cytoskeleton proteins in astrocytes and neurons of young rats at early stages (30 min) after infusion. Intrastriatal QA injection is an excitotoxic model of Huntington´s Disease (HD). Results showed that QA (150¿mol/0.5¿L) significantly increased the in vitro phosphorylation of the low molecular weight neurofilament subunit (NF-L) and the glial fibrillary acidic protein (GFAP) of neurons and astrocytes, respectively. This effect was mediated by cAMP-dependent protein kinase A (PKA), protein kinase C (PKC) and Ca2+/calmodulin-dependent protein kinase II (PKCaMII). In contrast, mitogen activated protein kinases (MAPK) were not activated by QA infusion. Furthermore, the specific N-methyl-D-aspartate (NMDA) antagonist MK-801 (0.25 mg/kg i.p), the antioxidant L-NAME (60 mg\kg\day), and diphenyldiselenide (PheSe)2 (0.625 mg\kg\day) injected prior to QA infusion totally prevented QA-induced hyperphosphorylation of cytoskeletal proteins. We also observed that QA-induced hyperphosphorylation was targeted at the Ser55 phosphorylating site on NF-L head domain, described as a regulatory site for NF assembly in vivo. This effect was fully prevented by MK801, by the PKA inhibitor H89 and by (PheSe)2, whereas staurosporine (PKC inhibitor) only partially prevented Ser55 phosphorylation. The PKCaMII inhibitor (KN93) and the antioxidant L-NAME failed to prevent the hyperphosphorylation of Ser55 by QA infusion. Therefore, we presume that QA-elicited NF-LSer55 hyperphosphorylation of the neural cytoskeleton achieved by intrastriatal QA injection could represent an early step in the pathophysiological cascade of deleterious events exerted by QA in rat striatum. Our observations also indicate that NMDA-mediated Ca2+ events and oxidative stress may be related to the altered protein cytoskeleton hyperphosphorylation observed with important implications for brain function.

ASSUNTO(S)

Ácido quinolínico citoesqueleto filamentos intermediários estresse oxidativo

Documentos Relacionados

• Efeito da administração intraestriatal aguda de ácido quinolínico sobre metabolismo energético em ratos jovens
• Efeitos da homocisteína sobre parâmetros bioquímicos e estruturais do citoesqueleto de células neurais de ratos
• Efeito da administração aguda intraestriatal do ácido alfa-ceto-isocapróico sobre parâmetros de estresse oxidativo em ratos jovens
• Administração intra-estriatal de ácido quinolínico inibe o metabolismo energético em estriado de ratos
• Efeitos da administração intraestriatal de lisina sobre parâmetros de estresse oxidativo e metabolismo energético em estriado de ratos jovens