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Circulating cell-free DNA methylation mirrors alterations in cerebral patterns in epilepsy

ABSTRACT: Circulating cell-free DNA methylation mirrors alterations in cerebral patterns in epilepsy

PROVIDER: PRJNA860960 | ENA |

REPOSITORIES: ENA

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Circulating cell-free DNA methylation mirrors alterations in cerebral patterns in epilepsy.

Project description:BackgroundDNA methylation profiling of circulating cell-free DNA (cfDNA) has rapidly become a promising strategy for biomarker identification and development. The cell-type-specific nature of DNA methylation patterns and the direct relationship between cfDNA and apoptosis can potentially be used non-invasively to predict local alterations. In addition, direct detection of altered DNA methylation patterns performs well as a biomarker. In a previous study, we demonstrated marked DNA methylation alterations in brain tissue from patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).ResultsWe performed DNA methylation profiling in cfDNA isolated from the serum of MTLE patients and healthy controls using BeadChip arrays followed by systematic bioinformatic analysis including deconvolution analysis and integration with DNase accessibility data sets. Differential cfDNA methylation analysis showed an overrepresentation of gene ontology terms and transcription factors related to central nervous system function and regulation. Deconvolution analysis of the DNA methylation data sets ruled out the possibility that the observed differences were due to changes in the proportional contribution of cortical neurons in cfDNA. Moreover, we found no overrepresentation of neuron- or glia-specific patterns in the described cfDNA methylation patterns. However, the MTLE-HS cfDNA methylation patterns featured a significant overrepresentation of the epileptic DNA methylation alterations previously observed in the hippocampus.ConclusionsOur results support the use of cfDNA methylation profiling as a rational approach to seeking non-invasive and reproducible epilepsy biomarkers.

| S-EPMC9795776 | biostudies-literature

Circulating cell-free DNA methylation mirrors alterations in cerebral patterns in epilepsy

Project description:DNA methylation progiling of circulaing cell-free DNA isolatated from serum of 12 MTLE patients and 11 healthy controls. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs.

2023-01-11 | GSE208758 | GEO

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

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

Cerebral palsy and epilepsy gut and oral microbiota

Project description:Cerebral palsy and epilepsy gut and oral microbiota Raw sequence reads

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Gut microbiome associated with epilepsy in children with cerebral palsy

Project description:Gut microbiome associated with epilepsy in children with cerebral palsy

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Photothrombotic Cerebral Stroke as a Model of Post-Stroke Seizures/Epilepsy in aged mice

Project description:Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility and brain injury using combined behavioral (video) and EEG monitoring and histological (MRI) assessments. To investigate GABAA receptor-mediated convulsive/non-convulsive seizures, lower-doses of pentylenetetrazol (PTZ) was injected. PTZ susceptibility in aging mice increased compared to young adults. One month after PT stroke, aged PT stroke mice exhibited severe convulsive seizures (late-onset). These findings exhibited the increase of GABAA receptor-mediated seizures susceptibility in PT stroke aging mice, but not in young adults.

2023-11-27 | GSE241528 | GEO

Circulating MicroRNAs From Serum Small Extracellular Vesicles as Potential diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy

Project description:Pediatric epilepsy is a neurological condition that causes repeated and unprovoked seizures and is more common in 1–5-year-old children. Drug resistance has been indicated as a key challenge in improving the clinical outcomes of patients with pediatric epilepsy. In the present study, we aimed to identify serum small extracellular vesicles (sEVs) derived microRNAs (miRNAs) from the serum samples of children for predicting the prognosis in patients with epilepsy and drug-resistant epilepsy

2022-01-20 | GSE193842 | GEO

Circulating MicroRNAs From Serum Small Extracellular Vesicles as Potential diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy

Project description:Circulating MicroRNAs From Serum Small Extracellular Vesicles as Potential diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy

| PRJNA798069 | ENA

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

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

| PRJNA978522 | ENA

Metabolic Adaptation in Epilepsy: From Acute Response to Chronic Impairment

Project description:Epilepsy is characterized by hypersynchronous neuronal discharges, which are associated with an increased cerebral metabolic rate of oxygen and ATP demand. Uncontrolled seizure activity (status epilepticus) results in mitochondrial exhaustion and ATP depletion, which potentially generate energy mismatch and neuronal loss. Many cells can adapt to increased energy demand by increasing metabolic capacities. However, acute metabolic adaptation during epileptic activity and its relationship to chronic epilepsy remains poorly understood. We elicited seizure-like events (SLEs) in an in vitro model of status epilepticus for eight hours. Electrophysiological recording and tissue oxygen partial pressure recordings were performed. After eight hours of ongoing SLEs, we used proteomics-based kinetic modeling to evaluate changes in metabolic capacities. We compared our findings regarding acute metabolic adaptation to published proteomic and transcriptomic data from chronic epilepsy patients. Epileptic tissue acutely responded to uninterrupted SLEs by upregulating ATP production capacity. This was achieved by a coordinated increase in the abundance of proteins from the respiratory chain and oxidative phosphorylation system. In contrast, chronic epileptic tissue shows a 25-40% decrease in ATP production capacity. In summary, our study reveals that epilepsy leads to dynamic metabolic changes. Acute epileptic activity boosts ATP production, while chronic epilepsy reduces it significantly.

2024-09-12 | PXD055090 | Pride

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