Plasma miRNAs as biomarkers of epilepsy
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ABSTRACT:
PROVIDER: PRJNA1009812 | ENA |
REPOSITORIES: ENA
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Project description:Epilepsy frequently develops as a result of brain insult, for example brain injury or stroke. Currently there are no tools allowing us to predict which trauma patients will eventually develop epilepsy. There is evidence that microRNAs levels are altered in plasma, making them attractive candidates for peripheral biomarkers of epilepsy. We analyzed miRNA levels in plasma samples using Affymetrix microarrays 4.1 and performed comparative analysis of samples. We performed 3 comparisons: i) control animals vs. Status epilepticus animals, ii) animals which developed first spontaneous seizure around 7 days post stimulation (EARLY), or later after 21days post stimulation (LATE), iii) animals that had developed seizures at given timepoint (EPI) and animals that did not experience seizures by given timepoint (NONEPI).
2023-12-10 | GSE241756 | GEO
Project description: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 Ago2-bound miRNAs in plasma samples collected from mice subject to status epilepticus (SE) 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.
2023-09-13 | GSE233890 | GEO
Project description:Purpose: Post-traumatic epilepsy (PTE) is an epilepsy that develops after traumatic brain injury (TBI), and it comprises 10-20% of structural epilepsies and 5% of all epilepsies. The lack of prognostic biomarkers for PTE hinders the development of anti-epileptogenic treatments. In this preclinical multicenter study, plasma samples collected from a rat model of PTE were analyzed by small RNA sequencing to reveal the post-TBI expression profile of circulating microRNAs and to identify potential miRNA biomarkers for PTE development. Methods: The animal experiments were conducted at 3 different study sites: University of Eastern Finland (Finland), Monash University (Australia), and University of California, Los Angeles (USA). Severe TBI was induced in adult male Sprague-Dawley rats by the lateral fluid-percussion injury (LFPI) method. Rats that developed PTE were identified by video-EEG monitoring during the 7th post-injury month (TBI rats with epilepsy, TBIE; TBI rats without epilepsy, TBIN). Small RNA sequencing was conducted with plasma samples collected 48 hours after TBI or sham operation (craniotomy). Following the primary quantification, DESeq2 (v. 1.42.0) was used to identify differentially expressed miRNAs between the experiment groups. Results were further validated in a larger sample cohort by droplet digital PCR (ddPCR). Results: Small RNA sequencing detected a total of 754 miRNAs that were expressed in at least one sample. DESeq2 detected 23 differentially expressed (DE) miRNAs between the TBI and sham groups, 12 between the TBIE and sham groups, and 5 between the TBIN and sham groups. In contrast, no DE miRNAs were detected between the TBIE and TBIN groups. From the list of 23 DE miRNAs between the TBI and sham groups, 3 upregulated miRNAs (rno-miR-183-5p, rno-miR-323-3p, and miR-434-3p) were selected for further ddPCR validation. The list of miRNAs for validation was further complemented by 4 miRNAs (rno-miR-9a-3p, rno-miR-124-3p, rno-miR-132-3p, and rno-miR-212-3p), which were not differentially expressed in the DESeq2 analysis, but which we have previously detected to be acutely upregulated in TBI rat plasma. The validation was conducted with samples from the entire EpiBioS4Rx cohort [26 baseline samples, 45 sham, 164 TBI (32 TBIE, 132 TBIN)]. DdPCR analysis revealed that all 7 investigated miRNAs were upregulated in the TBI rats compared with the sham controls. No differences were detected between the rats with (TBIE) or without epilepsy (TBIN). In contrast, TBIE rats that had seizure clusters (severe PTE) had lower levels of plasma miR-212-3p compared with other TBI rats. Furthermore, elastic net regularized logistic regression (glmnet) analysis identified miR-212-3p and miR-132-3p as the optimal set to differentiate TBIE rats with seizure clusters from other TBI rats. Conclusions: The profile of circulating plasma microRNAs differed between TBI rats and sham controls. MiR-212-3p alone or in combination with miR-132-3p showed potential as prognostic biomarkers for development of severe PTE.
2024-12-12 | GSE279767 | GEO
Project description: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 and reliable detection in biofluids. Altered expression of circulating microRNAs has been reported in human epilepsy, but most studies collected samples from one clinical site, relied on a single platform for profiling or conducted minimal validation. We collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two different countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated in a large cohort of samples (>300 samples) that included patients with psychogenic non-epileptic seizures. After profiling, validation of the discovery cohort and validation in the larger patient groups we identified miR-27a-3p, miR-328-3p and miR-654-3p with strong TLE biomarker potential. Plasma levels of these microRNAs were regulated in the same direction in plasma from epileptic mice, and furthermore were not different to healthy controls in patients with psychogenic non-epileptic seizures. The biomarker potential was extended by determining microRNA copy number in plasma and we demonstrate rapid detection of these microRNAs using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Investigation of the molecular transport mechanism in plasma determined analysis of all three microRNAs within the exosome-enriched provided highest diagnostic accuracy while levels of Argonaute-bound miR-328-3p selectively increased in patient samples collected after seizures. In situ hybridization revealed the presence of miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics analysis predicted targets linked to growth factor signaling and apoptosis. Taken together, this study extends evidence for the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms.
2019-01-02 | GSE114874 | GEO
Project description: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 and reliable detection in biofluids. Altered expression of circulating microRNAs has been reported in human epilepsy, but most studies collected samples from one clinical site, relied on a single platform for profiling or conducted minimal validation. We collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two different countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated in a large cohort of samples (>300 samples) that included patients with psychogenic non-epileptic seizures. After profiling, validation of the discovery cohort and validation in the larger patient groups we identified miR-27a-3p, miR-328-3p and miR-654-3p with strong TLE biomarker potential. Plasma levels of these microRNAs were regulated in the same direction in plasma from epileptic mice, and furthermore were not different to healthy controls in patients with psychogenic non-epileptic seizures. The biomarker potential was extended by determining microRNA copy number in plasma and we demonstrate rapid detection of these microRNAs using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Investigation of the molecular transport mechanism in plasma determined analysis of all three microRNAs within the exosome-enriched provided highest diagnostic accuracy while levels of Argonaute-bound miR-328-3p selectively increased in patient samples collected after seizures. In situ hybridization revealed the presence of miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics analysis predicted targets linked to growth factor signaling and apoptosis. Taken together, this study extends evidence for the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms.
2019-01-02 | GSE114847 | GEO
Project description: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 and reliable detection in biofluids. Altered expression of circulating microRNAs has been reported in human epilepsy, but most studies collected samples from one clinical site, relied on a single platform for profiling or conducted minimal validation. We collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two different countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated in a large cohort of samples (>300 samples) that included patients with psychogenic non-epileptic seizures. After profiling, validation of the discovery cohort and validation in the larger patient groups we identified miR-27a-3p, miR-328-3p and miR-654-3p with strong TLE biomarker potential. Plasma levels of these microRNAs were regulated in the same direction in plasma from epileptic mice, and furthermore were not different to healthy controls in patients with psychogenic non-epileptic seizures. The biomarker potential was extended by determining microRNA copy number in plasma and we demonstrate rapid detection of these microRNAs using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Investigation of the molecular transport mechanism in plasma determined analysis of all three microRNAs within the exosome-enriched provided highest diagnostic accuracy while levels of Argonaute-bound miR-328-3p selectively increased in patient samples collected after seizures. In situ hybridization revealed the presence of miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics analysis predicted targets linked to growth factor signaling and apoptosis. Taken together, this study extends evidence for the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms. microRNA expression in the plasma of 16 patients with TLE, before and after seizure, and 16 controls was measured by TaqMan OpenArray Human MicroRNA Panel.
2019-01-02 | GSE114700 | GEO
Project description: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 and reliable detection in biofluids. Altered expression of circulating microRNAs has been reported in human epilepsy, but most studies collected samples from one clinical site, relied on a single platform for profiling or conducted minimal validation. We collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two different countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated in a large cohort of samples (>300 samples) that included patients with psychogenic non-epileptic seizures. After profiling, validation of the discovery cohort and validation in the larger patient groups we identified miR-27a-3p, miR-328-3p and miR-654-3p with strong TLE biomarker potential. Plasma levels of these microRNAs were regulated in the same direction in plasma from epileptic mice, and furthermore were not different to healthy controls in patients with psychogenic non-epileptic seizures. The biomarker potential was extended by determining microRNA copy number in plasma and we demonstrate rapid detection of these microRNAs using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Investigation of the molecular transport mechanism in plasma determined analysis of all three microRNAs within the exosome-enriched provided highest diagnostic accuracy while levels of Argonaute-bound miR-328-3p selectively increased in patient samples collected after seizures. In situ hybridization revealed the presence of miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics analysis predicted targets linked to growth factor signaling and apoptosis. Taken together, this study extends evidence for the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms. microRNA expression in the plasma of 16 patients with TLE, before and after seizure, and 16 controls was measured by TaqMan OpenArray Human MicroRNA Panel.
2019-01-02 | GSE114697 | GEO
Project description:More and more studies have showed that plasma exosomal miRNAs are biomarkers for disease. The aim of the study were to investigate the miRNA profiling in plasma exosomes of patients with segmental vitiligo (SV) and to find biomarkers in plasma exosomes for patients with SV. Plasma exosomes and exosomal RNA of 7 SV patients and 8 health persons were purified by exoRNeasy Serum/Plasma Maxi Kit. The miRNA profiles of the 15 samples were sequenced using HiSeq 2500 (Illumina) and analyzed by Reads Per Million (RPM) values and edgeR algorithm. Some differently expressed miRNAs in plasma exosomes and skin tissues of the two sets were validated by qRT–PCR.A total of 85 miRNAs in plasma exosomes showed differential expression between SV patients and health persons, with a |log2（Fold Change）|≥1 and P-value < 0.05. Several miRNAs were confirmed by qRT–PCR and showed similar expression patterns between plasma exosomes and skin tissues. Our study depict the miRNAs expression profiles in plasma exosomes of SV patients and suggest that several miRNAs in plasma exosomes may serve as biomarkers for SV.
2022-03-24 | GSE198956 | GEO
Project description:Blood miRNA as biomarkers of epilepsy
| PRJNA983778 | ENA
Project description:More and more studies have showed that plasma exosomal miRNAs are biomarkers for disease. The aim of the study were to investigate the miRNA profiling in plasma exosomes of patients with non-segmental vitiligo (NSV) and to find biomarkers in plasma exosomes for patients with NSV. Plasma exosomes and exosomal RNA of 10 NSV patients and 10 health persons were purified by exoRNeasy Serum/Plasma Maxi Kit. The miRNA profiles of the 20 samples were sequenced using HiSeq 2500 (Illumina) and analyzed by Reads Per Million (RPM) values and edgeR algorithm. Some differently expressed miRNAs in plasma exosomes and skin tissues of the two sets were validated by qRT–PCR.Several miRNAs were confirmed by qRT–PCR and showed similar expression patterns between plasma exosomes and skin tissues. Our study depict the miRNAs expression profiles in plasma exosomes of NSV patients and suggest that several miRNAs in plasma exosomes may serve as biomarkers for NSV.
2022-12-09 | GSE141655 | GEO