Antagomir‐mediated suppression of microRNA‐134 reduces kainic acid‐induced seizures in immature mice.
MicroRNAs are short non-coding RNAs that negatively regulate protein levels and perform important roles in establishing and maintaining neuronal network function. Previous studies in adult rodents have detected upregulation of microRNA-134 after prolonged seizures (status epilepticus) and demonstrated that silencing microRNA-134 using antisense oligonucleotides, termed antagomirs, has potent and long-lasting seizure-suppressive effects. Here we investigated whether targeting microRNA-134 can reduce or delay acute seizures in the immature brain. Status epilepticus was induced in 21 day-old (P21) male mice by systemic injection of 5 mg/kg kainic acid. This triggered prolonged electrographic seizures and select bilateral neuronal death within the CA3 subfield of the hippocampus. Expression of microRNA-134 and functional loading to Argonaute-2 was not significantly changed in the hippocampus after seizures in the model. Nevertheless, when levels of microRNA-134 were reduced by prior intracerebroventricular injection of an antagomir, kainic acid-induced seizures were delayed and less severe and mice displayed reduced neuronal death in the hippocampus. These studies demonstrate targeting microRNA-134 may have therapeutic applications for the treatment of seizures in children.
European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 602130
Science Foundation Ireland (13/IA/1891, 11/TIDA/B1988)
European Regional Development Fund
Irish Research Council (GOIPD/2014/566)
Science Foundation Ireland (17/TIDA/5002)
Marie Skłodowska-Curie Actions Individual Fellowship (H2020-MSCA-IF-2018 840262)
Marie Skłodowska-Curie Actions Individual Fellowship (H2020-MSCA-IF-2017 798644)
Science Foundation Ireland (SFI) under Grant Number 16/RC/3948
FutureNeuro industry partners
RCSI STAR PhD programme
Hoffman-La Roche Ltd
CommentsThe original article is available at https://www.nature.com/
Published CitationCampbell A, Morris G, Heller JP, Langa E, Brindley E, Worm J, Jensen MA, Miller MT, Henshall DC, Reschke CR. Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced seizures in immature mice. Scientific Reports. 2021;11(1):340.
Publication Date11 January 2021
- FutureNeuro Centre
- Physiology and Medical Physics
- Neurological and Psychiatric Disorders
- Published Version (Version of Record)