Type

Journal Article

Authors

David C Henshall
Catherine Mooney
Felix Rosenow
Norman Delanty
Hajo Hamer
Jochen H M Prehn
Robert J Forster
Elaine Spain
Hazel McArdle
Thomas Hill
and 6 others

Subjects

Microbiology

Topics
blood disease models animal case control design computational biology animals epilepsy temporal lobe transcriptome gene expression profiling biofluids biomarkers point of care mice noncoding rna humans gene regulatory networks status epilepticus micrornas serum case control studies diagnosis temporal lobe epilepsy genetics high throughput nucleotide sequencing dissociative seizures circulating microrna

Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy. (2018)

Abstract There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable detection in biofluids. Altered levels of circulating microRNAs have been reported in human epilepsy, but most studies collected samples from one clinical site, used a single profiling platform or conducted minimal validation. Using a case-control design, we collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated findings in a large (>250) cohort of samples that included patients with psychogenic non-epileptic seizures (PNES). After profiling and validation, we identified miR-27a-3p, miR-328-3p and miR-654-3p with biomarker potential. Plasma levels of these microRNAs were also changed in a mouse model of TLE but were not different to healthy controls in PNES patients. We determined copy number of the three microRNAs in plasma and demonstrate their rapid detection using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Analysis of the microRNAs within the exosome-enriched fraction provided high diagnostic accuracy while Argonaute-bound miR-328-3p selectively increased in patient samples after seizures. In situ hybridization localized miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics predicted targets linked to growth factor signaling and apoptosis. This study demonstrates the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms.
Collections Ireland -> University College Dublin -> College of Science
Ireland -> University College Dublin -> Computer Science Research Collection
Ireland -> Dublin City University -> PubMed
Ireland -> University College Dublin -> School of Computer Science

Full list of authors on original publication

David C Henshall, Catherine Mooney, Felix Rosenow, Norman Delanty, Hajo Hamer, Jochen H M Prehn, Robert J Forster, Elaine Spain, Hazel McArdle, Thomas Hill and 6 others

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Catherine Mooney
University College Dublin
Total Publications: 63
 
3
Felix Rosenow
Royal College of Surgeons in Ireland
Total Publications: 8
 
4
Norman Delanty
Royal College of Surgeons in Ireland
Total Publications: 49
 
5
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
6
Robert J. Forster
Dublin City University
Total Publications: 92
 
7
Elaine Spain
Dublin City University
Total Publications: 15
 
8
Hazel McArdle
Dublin City University
Total Publications: 6