Cristina R. Reschke, Luiz F. Almeida Silva, Braxton A. Norwood, Ketharini Senthilkumar, Gareth Morris, Amaya Sanz-Rodriguez, Ronan M. Conroy, Lara Costard, Valentin Neubert, Sebastian Bauer, Michael A. Farrell, Donncha F. O'Brien, Norman Delanty, Stephanie Schorge, Ronald Jeroen Pasterkamp, Felix Rosenow, David C. Henshall
- Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus. Translation of these findings would benefit from evidence of efficacy in non-status epilepticus models and validation in another species. Here, we report that electrographic seizures and convulsive behavior are strongly reduced in adult mice pre-treated with Ant-134 in the pentylenetetrazol model. Pre-treatment with Ant-134 did not affect the severity of status epilepticus induced by perforant pathway stimulation in adult rats, a toxin-free model of acquired epilepsy. Nevertheless, Ant-134 post-treatment reduced the number of rats developing spontaneous seizures by 86% in the perforant pathway stimulation model and Ant-134 delayed epileptiform activity in a rat ex vivo hippocampal slice model. The potent anticonvulsant effects of Ant-134 in multiple models may encourage pre-clinical development of this approach to epilepsy therapy.
MetadatenAuthor: | Cristina R. Reschke, Luiz F. Almeida Silva, Braxton A. Norwood, Ketharini Senthilkumar, Gareth MorrisORCiD, Amaya Sanz-Rodriguez, Ronan M. Conroy, Lara Costard, Valentin Neubert, Sebastian BauerORCiDGND, Michael A. Farrell, Donncha F. O'Brien, Norman Delanty, Stephanie Schorge, Ronald Jeroen Pasterkamp, Felix RosenowORCiDGND, David C. HenshallORCiD |
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URN: | urn:nbn:de:hebis:30:3-431735 |
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DOI: | https://doi.org/10.1016/j.omtn.2016.11.002 |
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ISSN: | 2162-2531 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28325299 |
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Parent Title (English): | Molecular therapy. Nucleic Acids |
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Publisher: | Nature Publ. Group |
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Place of publication: | New York, NY |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2017/04/06 |
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Date of first Publication: | 2017/03/17 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2017/04/06 |
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Tag: | anti-epileptic drug; chemoconvulsant; epileptogenesis; hippocampal sclerosis; noncoding RNA; status epilepticus; temporal lobe epilepsy |
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Volume: | 6 |
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Page Number: | 12 |
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First Page: | 45 |
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Last Page: | 56 |
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Note: | © 2016 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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HeBIS-PPN: | 428658881 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
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