s41598-020-79350-7-2.pdf (12.58 MB)
Download file

Antagomir‐mediated suppression of microRNA‐134 reduces kainic acid‐induced seizures in immature mice.

Download (12.58 MB)
journal contribution
posted on 06.03.2021, 11:01 authored by Aoife Campbell, Gareth Morris, Janosch Heller, Elena Langa, Elizabeth Brindley, Jesper Worm, Mads Aaboe Jensen, Meghan T. Miller, David HenshallDavid Henshall, Cristina Ruedell ReschkeCristina Ruedell Reschke

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.

Funding

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

History

Comments

The original article is available at https://www.nature.com/

Published Citation

Campbell 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 Date

11 January 2021

PubMed ID

33431894

Department/Unit

  • FutureNeuro Centre
  • Physiology and Medical Physics

Research Area

  • Neurological and Psychiatric Disorders

Publisher

Springer Nature

Version

  • Published Version (Version of Record)