Epigenética y epilepsia

Fontes, L. Pulido; Jimenez, P. Quesada; Mendioroz, Maite

doi:10.1016/j.nrl.2014.03.012

Cited by 14 publications

(8 citation statements)

References 38 publications

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“…Such changes could affect susceptibility to and development/maintenance of epilepsy. In fact, the detection of epigenetic modifications observed in both animal models and tissues from patients with temporal lobe epilepsy are encouraging a new line of research that may contribute substantially to our knowledge of epilepsy susceptibility[115]. The significant challenge is how to apply these approaches to investigate risk factors in IGE epilepsy, such as JME.…”

Section: Discussionmentioning

confidence: 99%

Genetic susceptibility in Juvenile Myoclonic Epilepsy: Systematic review of genetic association studies

et al. 2017

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BackgroundSeveral genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we evaluate the accumulating findings and provide an updated perspective of these studies.MethodologyA systematic literature search was conducted using the PubMed, Embase, Scopus, Lilacs, epiGAD, Google Scholar and Sigle up to February 12, 2016. The quality of the included studies was assessed by a score and classified as low and high quality. Beyond outcome measures, information was extracted on the setting for each study, characteristics of population samples and polymorphisms.ResultsFifty studies met eligibility criteria and were used for data extraction. With a single exception, all studies used a candidate gene approach, providing data on 229 polymorphisms in or near 55 different genes. Of variants investigating in independent data sets, only rs2029461 SNP in GRM4, rs3743123 in CX36 and rs3918149 in BRD2 showed a significant association with JME in at least two different background populations. The lack of consistent associations might be due to variations in experimental design and/or limitations of the approach.ConclusionsThus, despite intense research evidence established, specific genetic variants in JME susceptibility remain inconclusive. We discussed several issues that may compromise the quality of the results, including methodological bias, endophenotype and potential involvement of epigenetic factors.PROSPERO registration numberCRD42016036063

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Section: Discussionmentioning

confidence: 99%

Genetic susceptibility in Juvenile Myoclonic Epilepsy: Systematic review of genetic association studies

et al. 2017

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“…In addition, a hypothesis has been previously demonstrated that the aberrant alterations in gene expression results in aberrant hyperexcitability, which may cause repeated seizures . It is significant to note the epigenetic mechanisms previously delineated to characterize the development of drug resistance in epilepsy, during which the altered gene expression has a role to play during antiepileptic drug uptake . Here, our study highlighted the involvement of miR‐139‐5p in the translational suppression of MRP1, resulting in the inhibition of drug resistance in refractory epilepsy.…”

Section: Discussionmentioning

confidence: 57%

microRNA‐139‐5p confers sensitivity to antiepileptic drugs in refractory epilepsy by inhibition of MRP1

et al. 2019

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Aim Drug resistance is an intractable issue urgently needed to be overcome for improving efficiency of antiepileptic drugs in treating refractory epilepsy. microRNAs (miRNAs) have been proved as key regulators and therapeutic targets in epilepsy. Accordingly, the aim of the present study was to identify a novel differentially expressed miRNA which could improve the efficiency of antiepileptic drugs during the treatment of refractory epilepsy. Methods and Results Serum samples were collected from children with refractory epilepsy. An in vivo refractory epilepsy model was developed in SD rats by electrical amygdala kindling. We identified that miR‐139‐5p was decreased and multidrug resistance‐associated protein 1 (MRP1) was remarkably upregulated in the serum samples from children with refractory epilepsy and the brain tissues from rat models of refractory epilepsy. After phenobarbitone injection in rat models of refractory epilepsy, the after discharging threshold in kindled amygdala was detected to screen out drug‐resistant rats. Dual‐luciferase reporter gene assay demonstrated that MRP1 was a target of miR‐139‐5p. In order to evaluate the effect of miR‐139‐5p/MRP1 axis on drug resistance of refractory epilepsy, we transfected plasmids into the hippocampus of drug‐resistant rats to alter the expression of miR‐139‐5p and MRP1. TUNEL staining and Nissl staining showed that miR‐139‐5p overexpression or MRP1 downregulation could reduce the apoptosis and promote survival of neurons, accompanied by alleviated neuronal damage. Conclusion Collectively, these results suggest an important role of miR‐139‐5p/MRP1 axis in reducing the resistance of refractory epilepsy to antiepileptic drugs.

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“…In addition, the neurodevelopment process also highly depends on DNA methylation (Gapp et al, 2014). Specifically, DNA methylation is observed at CpG islands in the mammalian genome, where it can modulate gene expression (Jones, 2012), through the addition of a methyl group to m 5 C molecules (Pulido Fontes et al, 2015). Brain DNA has one of the highest levels of m 5 Cs in human organs (Kriaucionis and Heintz, 2009; LaSalle et al, 2013), and DNA methylation is required for neuronal differentiation in mammals (Takizawa et al, 2001; Mohn et al, 2008).…”

Section: Canonical Epigenetics and Neurodevelopmentmentioning

confidence: 99%

Epigenetics in Neurodevelopment: Emerging Role of Circular RNA

Meng

Zhou

Feng

et al. 2019

Front. Cell. Neurosci.

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Canonical epigenetic modifications, including DNA methylation, histone modification and chromatin remodeling, play a role in numerous life processes, particularly neurodevelopment. Epigenetics explains the development of cells in an organism with the same DNA sequence into different cell types with various functions. However, previous studies on epigenetics have only focused on the chromatin level. Recently, epigenetic modifications of RNA, which mainly include 6-methyladenosine (m 6 A), pseudouridine, 5-methylcytidine (m 5 C), inosine (I), 2′- O -ribosemethylation, and 1-methyladenosine (m 1 A), have gained increasing attention. Circular RNAs (circRNAs), which are a type of non-coding RNA without a 5′ cap or 3′ poly (A) tail, are abundantly found in the brain and might respond to and regulate synaptic function. Also, circRNAs have various functions, such as microRNA sponge, regulation of gene transcription and interaction with RNA binding protein. In addition, circRNAs are methylated by N 6 -methyladenosine (m 6 A). In this review, we discuss the crucial roles of epigenetic modifications of circRNAs, such as m 6 A, in the genesis and development of neurons and in synaptic function and plasticity. Thus, this type of changes in circRNAs might be a therapeutic target in central nervous system (CNS) disorders and could aid the diagnosis and treatment of these disorders.

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Epigenética y epilepsia

Abstract: Identifying the epigenetic mechanisms involved in epilepsy is a promising line of research that will deliver more in-depth knowledge of epilepsy pathophysiology and treatments.

Cited by 14 publications

References 38 publications

Genetic susceptibility in Juvenile Myoclonic Epilepsy: Systematic review of genetic association studies

Genetic susceptibility in Juvenile Myoclonic Epilepsy: Systematic review of genetic association studies

microRNA‐139‐5p confers sensitivity to antiepileptic drugs in refractory epilepsy by inhibition of MRP1

Epigenetics in Neurodevelopment: Emerging Role of Circular RNA

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