Evidence map›Paper›PMID 31887157›Full record

ArticlePloS one2019

Neuronal and glial DNA methylation and gene expression changes in early epileptogenesis.

Toni C Berger, Magnus D Vigeland, Hanne S Hjorthaug, Lars Etholm, Cecilie G Nome, Erik Taubøll, Kjell Heuser, Kaja K Selmer

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.5field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 33 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Toni C BergerDepartment of Neurology, Oslo University Hospital, Oslo, Norway.ORCID 0000-0001-6279-6727
Magnus D VigelandDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Hanne S HjorthaugDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Lars EtholmNational Center for Epilepsy, Oslo University Hospital, Sandvika, Norway.
Cecilie G NomeUniversity of Oslo, Oslo, Norway.
Erik TaubøllDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Kjell HeuserDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Kaja K SelmerDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Oslo University Hospital · NOUniversity of Oslo · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsMesial Temporal Lobe Epilepsy is characterized by progressive changes of both neurons and glia, also referred to as epileptogenesis. No curative treatment options, apart from surgery, are available. DNA methylation (DNAm) is a potential upstream mechanism in epileptogenesis and may serve as a novel therapeutic target. To our knowledge, this is the first study to investigate epilepsy-related DNAm, gene expression (GE) and their relationship, in neurons and glia.

methodsWe used the intracortical kainic acid injection model to elicit status epilepticus. At 24 hours post injection, hippocampi from eight kainic acid- (KA) and eight saline-injected (SH) mice were extracted and shock frozen. Separation into neurons and glial nuclei was performed by flow cytometry. Changes in DNAm and gene expression were measured with reduced representation bisulfite sequencing (RRBS) and mRNA-sequencing (mRNAseq). Statistical analyses were performed in R with the edgeR package.

resultsWe observed fulminant DNAm- and GE changes in both neurons and glia at 24 hours after initiation of status epilepticus. The vast majority of these changes were specific for either neurons or glia. At several epilepsy-related genes, like HDAC11, SPP1, GAL, DRD1 and SV2C, significant differential methylation and differential gene expression coincided.

conclusionWe found neuron- and glia-specific changes in DNAm and gene expression in early epileptogenesis. We detected single genetic loci in several epilepsy-related genes, where DNAm and GE changes coincide, worth further investigation. Further, our results may serve as an information source for neuronal and glial alterations in both DNAm and GE in early epileptogenesis.

Indexed as

DNA MethylationGene Regulatory NetworksAnimalsDisease Models, AnimalEpigenesis, GeneticEpilepsy, Temporal LobeGalaninGene Expression ProfilingGene Expression RegulationGenetic Predisposition to DiseaseHistone DeacetylasesKainic AcidMaleMiceNeurogliaNeuronsDrd1 protein, mouseGalaninHdac11 protein, mouseHistone DeacetylasesKainic AcidOsteopontinReceptors, Dopamine D1Spp1 protein, mouse

Identifiers

PMID31887157
PMCPMC6936816
OpenAlexW2996886720

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.