Genome-wide microRNA profiling of plasma from three.....pdf (7.06 MB)

Genome-wide microRNA profiling of plasma from three different animal models identifies biomarkers of temporal lobe epilepsy

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posted on 26.04.2021, 15:55 by Gary P Brennan, Sebastian Bauer, Tobias Engel, Eva Jimenezmateos, Federico Del Gallo, Thomas DM Hill, Niamh Connolly, Lara Costard, Valentin Neubert, Beatrice Salvetti, Amaya Sanz Rodriguez, Mona Heiland, Omar Mamad, Elizabeth Brindley, Braxton Norwood, Aasia Batool, Rana Raoof, Hany El-Naggar, Cristina Ruedell Reschke, Norman Delanty, Jochen Prehn, Paolo Fabene, Catherine Mooney, Felix Rosenow, David Henshall
Epilepsy diagnosis is complex, requires a team of specialists and relies on in-depth patient and family history, MRI-imaging and EEG monitoring. There is therefore an unmet clinical need for a non-invasive, molecular-based, biomarker to either predict the development of epilepsy or diagnose a patient with epilepsy who may not have had a witnessed seizure. Recent studies have demonstrated a role for microRNAs in the pathogenesis of epilepsy. MicroRNAs are short non-coding RNA molecules which negatively regulate gene expression, exerting profound influence on target pathways and cellular processes. The presence of microRNAs in biofluids, ease of detection, resistance to degradation and functional role in epilepsy render them excellent candidate biomarkers. Here we performed the first multi-model, genome-wide profiling of plasma microRNAs during epileptogenesis and in chronic temporal lobe epilepsy animals. From video-EEG monitored rats and mice we serially sampled blood samples and identified a set of dysregulated microRNAs comprising increased miR-93-5p, miR-142-5p, miR-182-5p, miR-199a-3p and decreased miR-574-3p during one or both phases. Validation studies found miR-93-5p, miR-199a-3p and miR-574-3p were also dysregulated in plasma from patients with intractable temporal lobe epilepsy. Treatment of mice with common anti-epileptic drugs did not alter the expression levels of any of the five miRNAs identified, however administration of an anti-epileptogenic microRNA treatment prevented dysregulation of several of these miRNAs. The miRNAs were detected within the Argonuate2-RISC complex from both neurons and microglia indicating these miRNA biomarker candidates can likely be traced back to specific brain cell types. The current studies identify additional circulating microRNA biomarkers of experimental and human epilepsy which may support diagnosis of temporal lobe epilepsy via a quick, cost-effective rapid molecular-based test.

Funding

European Union Seventh Framework (FP7) “EpimiRNA” project under grant agreement 602130

MSCA IF “Epimirgen” 707530, CURE Taking Flight award

Science Foundation Ireland (SFI) under grant number 16/RC/3948

European Regional Development Fund and by FutureNeuro industry partners and grant number 13/IA/1891

Health Research Board HRA-POR-2015- 1243

Science Foundation Ireland (SFI) SIRG award 18/SIRG/5646

Science Foundation Ireland (SFI) 17/CDA/4708

History

Comments

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

Published Citation

Brennan GP, Bauer S, Engel T, Jimenez-Mateos EM, Del Gallo F, Hill TDM, Connolly NMC, Costard LS, Neubert V, Salvetti B, Sanz-Rodriguez A, Heiland M, Mamad O, Brindley E, Norwood B, Batool A, Raoof R, El-Naggar H, Reschke CR, Delanty N, Prehn JHM, Fabene P, Mooney C, Rosenow F, Henshall DC. Genome-wide microRNA profiling of plasma from three different animal models identifies biomarkers of temporal lobe epilepsy. Neurobiology of Disease. 2020;144:105048.

Publication Date

13 August 2020

PubMed ID

32800995

Department/Unit

  • Beaumont Hospital
  • FutureNeuro Centre
  • Physiology and Medical Physics
  • School of Pharmacy and Biomolecular Sciences
  • Anatomy and Regenerative Medicine

Research Area

  • Neurological and Psychiatric Disorders
  • Cancer
  • Biomaterials and Regenerative Medicine

Publisher

Elsevier

Version

  • Published Version (Version of Record)

Usage metrics

Royal College of Surgeons in Ireland

Licence

Exports