Your browser doesn't support javascript.
loading
Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy.
Schneider, Marius Frederik; Vogt, Miriam; Scheuermann, Johanna; Müller, Veronika; Fischer-Hentrich, Antje H L; Kremer, Thomas; Lugert, Sebastian; Metzger, Friedrich; Kudernatsch, Manfred; Kluger, Gerhard; Hartlieb, Till; Noachtar, Soheyl; Vollmar, Christian; Kunz, Mathias; Tonn, Jörg Christian; Coras, Roland; Blümcke, Ingmar; Pace, Claudia; Heinen, Florian; Klein, Christoph; Potschka, Heidrun; Borggraefe, Ingo.
Afiliación
  • Schneider MF; Division of Molecular Biology, Biomedical Center Munich, Ludwig Maximilians University, Munich, Germany.
  • Vogt M; International Max Planck Research School (IMPRS) for Molecular Life Sciences, Planegg-Martinsried, Germany.
  • Scheuermann J; ISAR Bioscience GmbH, Planegg, Germany.
  • Müller V; Division of Molecular Biology, Biomedical Center Munich, Ludwig Maximilians University, Munich, Germany.
  • Fischer-Hentrich AHL; Division of Molecular Biology, Biomedical Center Munich, Ludwig Maximilians University, Munich, Germany.
  • Kremer T; Munich Medical Research School, Ludwig Maximilians University, Munich, Germany.
  • Lugert S; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Metzger F; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Kudernatsch M; Versameb AG, Hochbergerstrasse 60C, 4057, Basel, Switzerland.
  • Kluger G; Clinic for Neurosurgery, Schoen-Klinik Vogtareuth, Germany.
  • Hartlieb T; Paracelsus Medical University, Salzburg, Austria.
  • Noachtar S; Paracelsus Medical University, Salzburg, Austria.
  • Vollmar C; Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schoen-Klinik Vogtareuth, Germany.
  • Kunz M; Paracelsus Medical University, Salzburg, Austria.
  • Tonn JC; Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schoen-Klinik Vogtareuth, Germany.
  • Coras R; Department of Neurology, Comprehensive Epilepsy Center, University Hospital of Munich, Ludwig Maximilians University, Munich, Germany.
  • Blümcke I; Department of Neurology, Comprehensive Epilepsy Center, University Hospital of Munich, Ludwig Maximilians University, Munich, Germany.
  • Pace C; Comprehensive Epilepsy Center, Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics, University Hospital of Munich, Ludwig Maximilians University, Munich, Germany.
  • Heinen F; Department of Neurosurgery, University Hospital of Munich, Ludwig Maximilians University, Munich, Germany.
  • Klein C; Department of Neurosurgery, University Hospital of Munich, Ludwig Maximilians University, Munich, Germany.
  • Potschka H; Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.
  • Borggraefe I; Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.
Transl Neurosci ; 15(1): 20220330, 2024 Jan 01.
Article en En | MEDLINE | ID: mdl-38283997
ABSTRACT

Objective:

Heterozygous mutations within the voltage-gated sodium channel α subunit (SCN1A) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of SCN1A are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches.

Methods:

We investigated SCN1A mRNA expression and expression of two SCN1A related antisense RNAs in brain tissues in different age groups of pediatric non-Dravet patients who underwent surgery for drug resistant epilepsy. The effect of different antisense oligonucleotides (ASOs) directed against SCN1A specific antisense RNAs on SCN1A expression was tested.

Results:

The SCN1A related antisense RNAs SCN1A-dsAS (downstream antisense, RefSeq identifier NR_110598) and SCN1A-usAS (upstream AS, SCN1A-AS, RefSeq identifier NR_110260) were widely expressed in the brain of pediatric patients. Expression patterns revealed a negative correlation of SCN1A-dsAS and a positive correlation of lncRNA SCN1A-usAS with SCN1A mRNA expression. Transfection of SK-N-AS cells with an ASO targeted against SCN1A-dsAS was associated with a significant enhancement of SCN1A mRNA expression and reduction in SCN1A-dsAS transcripts.

Conclusion:

These findings support the role of SCN1A-dsAS in the suppression of SCN1A mRNA generation. Considering the haploinsufficiency in genetic SCN1A related DS, SCN1A-dsAS is an interesting target candidate for the development of ASOs (AntagoNATs) based precision medicine therapeutic approaches aiming to enhance SCN1A expression in DS.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Transl Neurosci Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Transl Neurosci Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania