Down-regulation of RalBP1 expression reduces seizure threshold and synaptic inhibition in mice

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Title
Down-regulation of RalBP1 expression reduces seizure threshold and synaptic inhibition in mice
Author(s)
Young-Soo Bae; Woosuk Chung; Kihoon Han; Kyeong Yeol Park; Hosun Kim; Eunjoon Kim; Myoung-Hwan Kim
Publication Date
2013-04
Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.433, no.2, pp.175 - 180
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
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.
URI
https://pr.ibs.re.kr/handle/8788114/1356
ISSN
0006-291X
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > Journal Papers (저널논문)
Files in This Item:
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