| Autor: |
Cheah, Christine S., Yu, Frank H., Westenbroek, Ruth E., Kalume, Franck K., Oakley, John C., Potter, Gregory B., Rubenstein, John L., Catterall, William A. |
| Předmět: |
|
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 09/04/2012, Vol. 109 Issue 36, p14646-14651, 6p |
| Abstrakt: |
Heterozygous loss-of-function mutations in the brain sodium channel Nav1.1 cause Dravet syndrome (DS), a pharmacoresistant infantile-onset epilepsy syndrome with comorbidities of cognitive impairment and premature death. Previous studies using a mouse model of DS revealed reduced sodium currents and impaired excitability in GABAergic interneurons in the hippocampus, leading to the hypothesis that impaired excitability of GABAergic inhibitory neurons is the cause of epilepsy and premature death in DS. However, other classes of GABAergic interneurons are less impaired, so the direct cause of hyperexcitability, epilepsy, and premature death has remained unresolved. We generated a floxed Scnia mouse line and used the Cre-Lox method driven by an enhancer from the D/x1,2 locus for conditional deletion of Scnia in forebrain GABAergic neurons. Immunocytochemical studies demonstrated selective loss of Nav1.1 channels in GABAergic interneurons in cerebral cortex and hippocampus. Mice with this deletion died prematurely following generalized tonic-clonic seizures, and they were equally susceptible to thermal induction of seizures as mice with global deletion of Scnia. Evidently, loss of Nav1.1 channels in forebrain GABAergic neurons is both necessary and sufficient to cause epilepsy and premature death in DS. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
