Brain cell-specific origin of circulating microRNA biomarkers in experimental temporal lobe epilepsy

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Elizabeth Brindley¹  Aasia Batool¹  Mairead Diviney¹  Mona Heiland²  Karen Conboy²  Amaya Sanz-Rodriguez²  Thomas D. M. Hill²  Omar Mamad²  Elena Langa²  David C. Henshall²  Gareth Morris³  Janosch P. Heller⁴  Gary P. Brennan⁵  Catherine Mooney⁶  Cristina R. Reschke⁷  Jørgen Kjems⁸  Morten T. Venø⁹  Yan Yan⁹ 

[1] Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland;Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland;FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland;Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland;FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland;Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom;Division of Neuroscience, Faculty of Biology, Medicine and Health, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom;Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland;FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland;School of Biotechnology, Dublin City University, Dublin, Ireland;FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland;School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Dublin, Ireland;FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland;School of Computer Science, University College Dublin, Dublin, Ireland;FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland;School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland;Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark;Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark;Omiics ApS, Aarhus, Denmark;

关键词: electroencephalogram;    diagnosis;    epigenetic;    hippocampus;    noncoding RNA;    point-of-care testing;    temporal lobe epilepsy;   

DOI  :  10.3389/fnmol.2023.1230942

 received in 2023-05-29, accepted in 2023-09-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

The diagnosis of epilepsy is complex and challenging and would benefit from the availability of molecular biomarkers, ideally measurable in a biofluid such as blood. Experimental and human epilepsy are associated with altered brain and blood levels of various microRNAs (miRNAs). Evidence is lacking, however, as to whether any of the circulating pool of miRNAs originates from the brain. To explore the link between circulating miRNAs and the pathophysiology of epilepsy, we first sequenced argonaute 2 (Ago2)-bound miRNAs in plasma samples collected from mice subject to status epilepticus induced by intraamygdala microinjection of kainic acid. This identified time-dependent changes in plasma levels of miRNAs with known neuronal and microglial-cell origins. To explore whether the circulating miRNAs had originated from the brain, we generated mice expressing FLAG-Ago2 in neurons or microglia using tamoxifen-inducible Thy1 or Cx3cr1 promoters, respectively. FLAG immunoprecipitates from the plasma of these mice after seizures contained miRNAs, including let-7i-5p and miR-19b-3p. Taken together, these studies confirm that a portion of the circulating pool of miRNAs in experimental epilepsy originates from the brain, increasing support for miRNAs as mechanistic biomarkers of epilepsy.

【 授权许可】

Unknown   
Copyright © 2023 Brindley, Heiland, Mooney, Diviney, Mamad, Hill, Yan, Venø, Reschke, Batool, Langa, Sanz-Rodriguez, Heller, Morris, Conboy, Kjems, Brennan and Henshall.