Frontiers in Molecular Neuroscience (Sep 2023)
Brain cell-specific origin of circulating microRNA biomarkers in experimental temporal lobe epilepsy
- Elizabeth Brindley,
- Mona Heiland,
- Mona Heiland,
- Catherine Mooney,
- Catherine Mooney,
- Mairead Diviney,
- Omar Mamad,
- Omar Mamad,
- Thomas D. M. Hill,
- Thomas D. M. Hill,
- Yan Yan,
- Yan Yan,
- Morten T. Venø,
- Morten T. Venø,
- Cristina R. Reschke,
- Cristina R. Reschke,
- Aasia Batool,
- Elena Langa,
- Elena Langa,
- Amaya Sanz-Rodriguez,
- Amaya Sanz-Rodriguez,
- Janosch P. Heller,
- Janosch P. Heller,
- Janosch P. Heller,
- Gareth Morris,
- Gareth Morris,
- Gareth Morris,
- Gareth Morris,
- Karen Conboy,
- Karen Conboy,
- Jørgen Kjems,
- Gary P. Brennan,
- Gary P. Brennan,
- David C. Henshall,
- David C. Henshall
Affiliations
- Elizabeth Brindley
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Mona Heiland
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Mona Heiland
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Catherine Mooney
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Catherine Mooney
- School of Computer Science, University College Dublin, Dublin, Ireland
- Mairead Diviney
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Omar Mamad
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Omar Mamad
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Thomas D. M. Hill
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Thomas D. M. Hill
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Yan Yan
- Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
- Yan Yan
- Omiics ApS, Aarhus, Denmark
- Morten T. Venø
- Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
- Morten T. Venø
- Omiics ApS, Aarhus, Denmark
- Cristina R. Reschke
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Cristina R. Reschke
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Aasia Batool
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Elena Langa
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Elena Langa
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Amaya Sanz-Rodriguez
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Amaya Sanz-Rodriguez
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Janosch P. Heller
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Janosch P. Heller
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Janosch P. Heller
- School of Biotechnology, Dublin City University, Dublin, Ireland
- Gareth Morris
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Gareth Morris
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Gareth Morris
- Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
- Gareth Morris
- Division of Neuroscience, Faculty of Biology, Medicine and Health, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
- Karen Conboy
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Karen Conboy
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Jørgen Kjems
- Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
- Gary P. Brennan
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- Gary P. Brennan
- 0School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Dublin, Ireland
- David C. Henshall
- Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- David C. Henshall
- FutureNeuro SFI Research Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- DOI
- https://doi.org/10.3389/fnmol.2023.1230942
- Journal volume & issue
-
Vol. 16
Abstract
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.
Keywords
