Academic Journal
Potent Anti-seizure Effects of Locked Nucleic Acid Antagomirs Targeting miR-134 in Multiple Mouse and Rat Models of Epilepsy
| العنوان: | Potent Anti-seizure Effects of Locked Nucleic Acid Antagomirs Targeting miR-134 in Multiple Mouse and Rat Models of Epilepsy |
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| المؤلفون: | Cristina R. Reschke, Luiz F. Almeida Silva, Braxton A. Norwood, Ketharini Senthilkumar, Gareth Morris, Amaya Sanz-Rodriguez, Ronán M. Conroy, Lara Costard, Valentin Neubert, Sebastian Bauer, Michael A. Farrell, Donncha F. O’Brien, Norman Delanty, Stephanie Schorge, R. Jeroen Pasterkamp, Felix Rosenow, David C. Henshall |
| المصدر: | Molecular Therapy: Nucleic Acids, Vol 6, Iss , Pp 45-56 (2017) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2017 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Therapeutics. Pharmacology, RM1-950 |
| الوصف: | 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. Keywords: noncoding RNA, hippocampal sclerosis, epileptogenesis, chemoconvulsant, status epilepticus, anti-epileptic drug, temporal lobe epilepsy |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2162-2531 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2162253116303596; https://doaj.org/toc/2162-2531; https://doaj.org/article/964e0e9884114ff28a56f53b767ff970 |
| DOI: | 10.1016/j.omtn.2016.11.002 |
| الاتاحة: | https://doi.org/10.1016/j.omtn.2016.11.002 https://doaj.org/article/964e0e9884114ff28a56f53b767ff970 |
| رقم الانضمام: | edsbas.CBAF0B26 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 21622531 |
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| DOI: | 10.1016/j.omtn.2016.11.002 |