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

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posted on 06.03.2021, 11:01 by Aoife Campbell, Gareth Morris, Janosch Heller, Elena Langa, Elizabeth Brindley, Jesper Worm, Mads Aaboe Jensen, Meghan T. Miller, David Henshall, Cristina 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

RCSI STAR PhD programme

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

Hoffman-La Roche Ltd

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

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)

Licence

Exports

Royal College of Surgeons in Ireland

Categories

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Exports