Micro<scp>RNA</scp> and mesial temporal lobe epilepsy with hippocampal sclerosis: Whole mi<scp>RN</scp>ome profiling of human hippocampus

Bencúrová, Petra; Baloun, Jiří; Musilová, Kateřina; Radová, Lenka; Tichý, Boris; Pail, Martin; Zeman, M.; Brichtová, Eva; Hermanová, Markéta; Pospı́šilová, Šárka; Mráz, Marek; Brázdil, Milan

doi:10.1111/epi.13870

Cited by 44 publications

(51 citation statements)

References 40 publications

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“…Analyzing the literature to identify all the publications on whole miRNA profiling on human epileptic tissues (hippocampus or DG), we identified only one new recent paper that proposes the whole miRNA profile of human hippocampus of TLE subjects. 58 Considering the 20 tissue-isolated miRNAs in common between at least two TLE animal models obtained by an analysis of Table 1 (namely, miR-23a, miR-27a, miR-31, miR-99a, miR-125b-5p, miR-129-5p, miR-132-5p, miR-142-5p, miR-146a, miR-212-3p, and miR-375 all upregulated; miR-10b, miR-21, miR-29a, miR-138, miR-153, miR-181c, miR-187-3p, miR-330-3p, and miR-551b-3p all downregulated), we found some present in the profiles of human epileptic tissue. In particular, we found 4 miRNAs that are in common with the miRNA hippocampus profile of human TLE subjects.…”

Section: Main Textmentioning

confidence: 99%

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Potential Role of miRNAs as Theranostic Biomarkers of Epilepsy

Cava

Manna

Gambardella

et al. 2018

Molecular Therapy - Nucleic Acids

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Epilepsy includes a group of disorders of the brain characterized by an enduring predisposition to generate epileptic seizures. Although familial epilepsy has a genetic component and heritability, the etiology of the majority of non-familial epilepsies has no known associated genetic mutations. In epilepsy, recent epigenetic profiles have highlighted a possible role of microRNAs in its pathophysiology. In particular, molecular profiling identifies a significant number of microRNAs (miRNAs) altered in epileptic hippocampus of both animal models and human tissues. In this review, analyzing molecular profiles of different animal models of epilepsy, we identified a group of 20 miRNAs commonly altered in different epilepsy-animal models. As emerging evidences highlighted the poor overlap between signatures of animal model tissues and human samples, we focused our analysis on miRNAs, circulating in human biofluids, with a principal role in epilepsy hallmarks, and we identified a group of 8 diagnostic circulating miRNAs. We discussed the functional role of these 8 miRNAs in the epilepsy hallmarks. A few of them have also been proposed as therapeutic molecules for epilepsy treatment, revealing a great potential for miRNAs as theranostic molecules in epilepsy.

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Section: Main Textmentioning

confidence: 99%

“…In particular, we found 4 miRNAs that are in common with the miRNA hippocampus profile of human TLE subjects. 58 Following the new annotation suggested by the database http://mirgenedb.org/ , 59 the four miRNAs are Hsa-miR-132-P1, Hsa-miR-142-P1-v1_5p, Hsa-miR-146-P1_5p, and Hsa-miR-138-P1_5p.…”

Section: Main Textmentioning

confidence: 99%

Potential Role of miRNAs as Theranostic Biomarkers of Epilepsy

Cava

Manna

Gambardella

et al. 2018

Molecular Therapy - Nucleic Acids

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“…This indicates that Ago2-seq identifies robust miRNAs for targeting, a means to cross-compare between species and model, and a way to better prioritize miRNAs for functional assessment. A number of the miRNAs reported to be dysregulated in human TLE 52–54 were also differentially expressed in the chronic epilepsy state. This underscores the clinical relevance and translatability of our findings.…”

Section: Discussionmentioning

confidence: 99%

Ago2-seq identifies new microRNA targets for seizure control

Reschke

Morris

Connolly

et al. 2019

Preprint

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36MicroRNAs (miRNAs) are short noncoding RNAs that shape the gene expression landscape, 37 including during the pathogenesis of temporal lobe epilepsy (TLE). In order to provide a full 38 catalog of the miRNA changes that happen during experimental TLE, we sequenced 39Argonaute 2-loaded miRNAs in the hippocampus of three different animal models at regular 40 intervals between the time of the initial precipitating insult to the establishment of 41 spontaneous recurrent seizures. The commonly upregulated miRNAs were selected for a 42 functional in vivo screen using oligonucleotide inhibitors. This revealed anti-seizure 43 phenotypes upon inhibition of miR-10a-5p, miR-21a-5p and miR-142a-5p as well as 44 neuroprotection-only effects for inhibition of miR-27a-3p and miR-431-5p. Proteomic data 45 and pathway analysis on predicted and validated targets of these miRNAs indicated a role for 46TGFβ signaling in a shared seizure-modifying mechanism. Together, these results identify 47 functional miRNAs in the hippocampus and a pipeline of new targets for seizure control in 48 epilepsy. 49 50

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“…These factors might affect the miRNA composition of the hippocampal tissue (Crespo et al, 2018) and cause inter-individual variability in both control and patient groups. Another discussed drawback is the origin of control brain tissues, which mostly come from postmortem autopsies, however, previous research discovered virtually unchanged miRNA composition in postmortem tissues within 30 h after death (Kakimoto et al, 2015;Bencurova et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Epilepsy miRNA Profile Depends on the Age of Onset in Humans and Rats

et al. 2020

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Temporal lobe epilepsy (TLE) is a severe neurological disorder accompanied by recurrent spontaneous seizures. Although the knowledge of TLE onset is still incomplete, TLE pathogenesis most likely involves the aberrant expression of microRNAs (miRNAs). miRNAs play an essential role in organism homeostasis and are widely studied in TLE as potential therapeutics and biomarkers. However, many discrepancies in discovered miRNAs occur among TLE studies due to model-specific miRNA expression, different onset ages of epilepsy among patients, or technology-related bias. We employed a massive parallel sequencing approach to analyze brain tissues from 16 adult mesial TLE (mTLE)/hippocampal sclerosis (HS) patients, 8 controls and 20 rats with TLElike syndrome, and 20 controls using the same workflow and categorized these subjects based on the age of epilepsy onset. All categories were compared to discover overlapping miRNAs with an aberrant expression, which could be involved in TLE. Our cross-comparative analyses showed distinct miRNA profiles across the age of epilepsy onset and found that the miRNA profile in rats with adult-onset TLE shows the closest resemblance to the profile in mTLE/HS patients. Additionally, this analysis revealed overlapping miRNAs between patients and the rat model, which should participate in epileptogenesis and ictogenesis. Among the overlapping miRNAs stand out miR-142-5p and miR-142-3p, which regulate immunomodulatory agents with pro-convulsive effects and suppress neuronal growth. Our cross-comparison study enhanced the insight into the effect of the age of epilepsy onset on miRNA expression and deepened the knowledge of epileptogenesis. We employed the same methodological workflow in both patients and the rat model, thus improving the reliability and accuracy of our results.

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MicroRNA and mesial temporal lobe epilepsy with hippocampal sclerosis: Whole miRNome profiling of human hippocampus

Cited by 44 publications

References 40 publications

Potential Role of miRNAs as Theranostic Biomarkers of Epilepsy

Potential Role of miRNAs as Theranostic Biomarkers of Epilepsy

Ago2-seq identifies new microRNA targets for seizure control

Epilepsy miRNA Profile Depends on the Age of Onset in Humans and Rats

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