Epileptiform discharge upregulates p-ERK1/2, growth-associated protein 43 and synaptophysin in cultured rat hippocampal neurons.
Seizure
; 18(10): 680-5, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19819736
ABSTRACT
Extracellular signal-regulated protein kinase, ERK1/2 is activated by phosphorylation (p-ERK1/2) during environmental stress such as epileptiform discharge. We investigated the role of ERK1/2 in abnormal axon growth and synapse reorganization in cultured neurons displaying epileptiform activity. The cultured neurons displaying epileptiform activity were treated with magnesium-free extracellular fluid for 3h and monitored epileptiform discharges using whole-cell patch clamp. Two study groups, neurons displaying epileptiform activity and the same neurons treated with ERK1/2 inhibitor U0126, were studied at six time points, 0 min, 30 min, 2h, 6h, 12h, and 24h following discharge. The expressions of p-ERK1/2, C-fos, growth-associated protein 43 (GAP-43) and synaptophysin (SYP), as markers of axon growth and synapse reorganization, were investigated by double-label immunofluorescence and western blotting. In the neurons displaying epileptiform activity, p-ERK1/2 was detected immediately following discharge, and expression peaked at 30 min. The expression of C-fos, GAP-43 and SYP followed the same pattern as p-ERK1/2. In the treated group, p-ERK1/2 was inhibited completely, and C-fos, GAP-43 and SYP were reduced. These findings indicate that epileptiform discharge activates ERK1/2 which regulates C-fos in cultured neurons displaying epileptiform activity, and this cascade may upregulate GAP-43 and SYP to contribute to axon growth and synapse reorganization to potentiate epileptic activities.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
/
Sinaptofisina
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Proteína GAP-43
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MAP Quinases Reguladas por Sinal Extracelular
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Hipocampo
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Neurônios
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article