Antagomirs and microRNA in status epilepticus

Abstract

MicroRNAs are an important class of noncoding RNA, which function as posttranscriptional regulators of protein levels within cells. Emerging work has revealed that status epilepticus produces select changes to microRNA levels within the brain, which may impact levels of proteins involved in neuronal structure and excitability, gliosis, inflammation, and apoptosis. Animal studies show that targeting microRNAs using locked nucleic acid-modified oligonucleotides ("antagomirs") can have potent effects on status epilepticus, seizure-induced neuronal death, and the later emergence of recurrent spontaneous seizures. Accordingly, microRNA-based therapeutics may have potential as a future treatment of status epilepticus.

Keywords: Epilepsy; Epileptogenesis; Hippocampal sclerosis; Noncoding RNA.

Figure 1

Post-treatment with antagomirs reduces later spontaneous seizures. Mice were injected with antagomirs targeting miR-134 (Ant-134) or a non-targeting scrambled control (Scram) 1 h after triggering status epilepticus and then epilepsy monitoring commenced. Graph shows box-and-whisker plots of data on telemetry (weeks 1-2) and video-monitored (weeks 3-4) spontaneous seizures in mice (n = 5-6 per group; *p < 0.05). Data are adapted from Jimenez-Mateos et al. (2012)