Down-regulation of RalBP1 expression reduces seizure threshold and synaptic inhibition in mice.
Biochem Biophys Res Commun
; 433(2): 175-80, 2013 Apr 05.
Article
em En
| MEDLINE
| ID: mdl-23485460
ABSTRACT
Idiopathic epilepsy is characterized by seizures without a clear etiology and is believed to have a strong genetic component but exhibits a complex inheritance pattern. Genetic factors seem to confer a low seizure threshold to susceptible individuals and thereby enhance epileptogenesis. However, the identity of susceptibility genes and the mechanisms regulating seizure threshold are still poorly understood. Here, we describe that reduced expression of RalBP1, a downstream effector of the small GTPases RalA and RalB, lowers the seizure threshold in mice. The intraperitoneal injection of the chemoconvulsant pentylenetetrazol induced more severe seizures in RalBP1 hypomorphic mice than in their wild-type littermates. The reduction of RalBP1 in the brain has no effect on neuronal excitability, but does decrease the inhibitory synaptic transmission onto CA1 pyramidal neurons. This impaired synaptic inhibition was associated with the loss of GABAergic interneurons in the CA1 subfield of the hippocampus. The present study identifies RalBP1 as a gene regulating the seizure threshold in mice and provides direct evidence for the role of RalBP1 in synaptic inhibition in vivo.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Convulsões
/
Transmissão Sináptica
/
Proteínas Ativadoras de GTPase
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2013
Tipo de documento:
Article