Type

Other / n/a

Authors

David C Henshall
Felix Rosenow
R Jeroen Pasterkamp
Stephanie Schorge
Norman Delanty
Donncha F O'Brien
Michael A Farrell
Sebastian Bauer
Valentin Neubert
Lara Costard
and 7 others

Subjects

Psychiatry

Topics
physiology anti epileptic drug physics chemoconvulsant temporal lobe epilepsy noncoding rna hippocampal sclerosis epileptogenesis status epilepticus

Potent Anti-seizure Effects of Locked Nucleic Acid Antagomirs Targeting miR-134 in Multiple Mouse and Rat Models of Epilepsy. (2017)

Abstract 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.
Collections Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Epidemiology and Public Health Medicine
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics
Ireland -> Royal College of Surgeons in Ireland -> Epidemiology and Public Health Medicine Articles
Ireland -> Royal College of Surgeons in Ireland -> Division of Population Health Sciences

Full list of authors on original publication

David C Henshall, Felix Rosenow, R Jeroen Pasterkamp, Stephanie Schorge, Norman Delanty, Donncha F O'Brien, Michael A Farrell, Sebastian Bauer, Valentin Neubert, Lara Costard and 7 others

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Felix Rosenow
Royal College of Surgeons in Ireland
Total Publications: 8
 
3
R Jeroen Pasterkamp
Royal College of Surgeons in Ireland
Total Publications: 3
 
4
Stephanie Schorge
Royal College of Surgeons in Ireland
Total Publications: 3
 
5
Norman Delanty
Royal College of Surgeons in Ireland
Total Publications: 49
 
6
Donncha F O'Brien
Royal College of Surgeons in Ireland
Total Publications: 19
 
7
Michael A Farrell
Royal College of Surgeons in Ireland
Total Publications: 43
 
8
Sebastian Bauer
Royal College of Surgeons in Ireland
Total Publications: 7