Reschke, Cristina R. Silva, Luiz FA Norwood, Braxton A. Senthilkumar, Ketharini Morris, Gareth Sanz-Rodriguez, Amaya Conroy, RonĂ¡n Costard, Lara Neubert, Valentin Bauer, Sebastian Farrell, Michael A. O'Brien, Donncha F. Delanty, Norman Schorge, Stephanie Pasterkamp, R Jeroen Rosenow, Felix Henshall, David C. Potent Anti-seizure Effects of Locked Nucleic Acid Antagomirs Targeting miR-134 in Multiple Mouse and Rat Models of Epilepsy. <p>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.</p> Anti-epileptic drug;chemoconvulsant;epileptogenesis;hippocampal sclerosis;noncoding RNA;status epilepticus;temporal lobe epilepsy.;Physiology;Medical Physics 2019-11-22
    https://repository.rcsi.com/articles/journal_contribution/Potent_Anti-seizure_Effects_of_Locked_Nucleic_Acid_Antagomirs_Targeting_miR-134_in_Multiple_Mouse_and_Rat_Models_of_Epilepsy_/10793789