Delayed maturation of GABAergic signaling in the Scn1a and Scn1b mouse models of Dravet Syndrome.
Sci Rep
; 9(1): 6210, 2019 04 17.
Article
em En
| MEDLINE
| ID: mdl-30996233
ABSTRACT
Dravet syndrome (DS) is a catastrophic developmental and epileptic encephalopathy characterized by severe, pharmacoresistant seizures and the highest risk of Sudden Unexpected Death in Epilepsy (SUDEP) of all epilepsy syndromes. Here, we investigated the time course of maturation of neuronal GABAergic signaling in the Scn1b-/- and Scn1a+/- mouse models of DS. We found that GABAergic signaling remains immature in both DS models, with a depolarized reversal potential for GABAA-evoked currents compared to wildtype in the third postnatal week. Treatment of Scn1b-/- mice with bumetanide resulted in a delay in SUDEP onset compared to controls in a subset of mice, without prevention of seizure activity or amelioration of failure to thrive. We propose that delayed maturation of GABAergic signaling may contribute to epileptogenesis in SCN1B- and SCN1A-linked DS. Thus, targeting the polarity of GABAergic signaling in brain may be an effective therapeutic strategy to reduce SUDEP risk in DS.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Epilepsias Mioclônicas
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Canal de Sódio Disparado por Voltagem NAV1.1
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Subunidade beta-1 do Canal de Sódio Disparado por Voltagem
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Ácido gama-Aminobutírico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2019
Tipo de documento:
Article