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Neurosci Lett ; 572: 20-5, 2014 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-24810882

RESUMEN

Status epilepticus (SE) is a life-threatening neurological disorder associated with significant morbidity and mortality. MicroRNAs (miRNAs) are small, non-coding RNAs that act post-transcriptionally modulating messenger RNA (mRNA) translation or stability which may have important roles in the pathogenesis of epilepsy. It has been reported that silencing microRNA-134 in vivo has significant neuroprotective and prolonged seizure-suppressive effects. However, the mechanism by which miR-134 inhibition suppressed seizures and whether miR-134 inhibition works in an in vitro model of SE, is unknown. Compared to a complex in vivo system, in vitro models of SE-like electrographic activity can be powerful tools to study this miRNA. Using a cell culture model of low Mg(2+) treatment of rat hippocampal neurons, we found SE-like electrographic activity increased expression of miR-134. Inhibiting expression of miR-134 using an inhibitor lentivirus with two miR-134 binding sites reduced SE-like electrographic activity in the hippocampal neurons and reduced neuronal death. This study provides direct evidence that inhibition of miR-134 can block status epilepticus-like discharges and is neuroprotective in hippocampal neuronal cultures and implies that inhibiting miR-134 may be a potential candidate for the clinical treatment of SE.


Asunto(s)
Hipocampo/fisiopatología , MicroARNs/genética , Neuronas/fisiología , Estado Epiléptico/fisiopatología , Animales , Hipocampo/metabolismo , Lentivirus/genética , Quinasas Lim/metabolismo , MicroARNs/metabolismo , Cultivo Primario de Células , Ratas Sprague-Dawley , Estado Epiléptico/metabolismo
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