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Epilepsy microRNA

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https://www.readbyqxmd.com/read/28384161/microrna-hsa-mir-134-is-a-circulating-biomarker-for-mesial-temporal-lobe-epilepsy
#1
Simoni H Avansini, Beatriz Pereira de Sousa Lima, Rodrigo Secolin, Marilza L Santos, Ana Carolina Coan, André S Vieira, Fábio R Torres, Benilton S Carvalho, Marina K M Alvim, Márcia E Morita, Clarissa L Yasuda, Luciana R Pimentel-Silva, Danyella B Dogini, Fabio Rogerio, Fernando Cendes, Iscia Lopes-Cendes
Epilepsy is misdiagnosed in up to 25% of patients, leading to serious and long-lasting consequences. Recently, circulating microRNAs have emerged as potential biomarkers in a number of clinical scenarios. The purpose of this study was to identify and to validate circulating microRNAs that could be used as biomarkers in the diagnosis of epilepsy. Quantitative real-time PCR was used to measure plasma levels of three candidate microRNAs in two phases of study: an initial discovery phase with 14 patients with mesial temporal lobe epilepsy (MTLE), 13 with focal cortical dysplasia (FCD) and 16 controls; and a validation cohort constituted of an independent cohort of 65 patients with MTLE and 83 controls...
2017: PloS One
https://www.readbyqxmd.com/read/28382310/reply-to-is-a-microrna-328-binding-site-in-pax6-associated-with-rolandic-epilepsy
#2
Lisa J Strug, Deb K Pal
No abstract text is available yet for this article.
April 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28382309/is-a-microrna-328-binding-site-in-pax6-associated-with-rolandic-epilepsy
#3
Amelia McGlade, Kenneth A Myers, Samuel F Berkovic, Ingrid E Scheffer, Slavé Petrovski, Michael S Hildebrand
No abstract text is available yet for this article.
April 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28331471/manipulating-micrornas-in-murine-models-targeting-the-multi-targeting-in-epilepsy
#4
David C Henshall
MicroRNAs are small noncoding RNAs that work posttranscriptionally to negatively regulate protein levels. They influence neuronal and glial structure and function, neuroinflammatory signaling, cell death, neurogenesis, and other processes relevant to epileptogenesis. Functional studies using oligonucleotide inhibitors (antagomirs) and mimics (agomirs) to modulate microRNAs in rat and mouse models of epilepsy show effects on evoked and spontaneous seizures and attendant neuropathology. The present review summarizes recent findings and points to gaps in our knowledge of the underlying mechanisms and directions for the future...
January 2017: Epilepsy Currents
https://www.readbyqxmd.com/read/28325299/potent-anti-seizure-effects-of-locked-nucleic-acid-antagomirs-targeting-mir-134-in-multiple-mouse-and-rat-models-of-epilepsy
#5
Cristina R Reschke, Luiz F Almeida Silva, Braxton A Norwood, Ketharini Senthilkumar, Gareth Morris, Amaya Sanz-Rodriguez, Ronán M Conroy, Lara Costard, Valentin Neubert, Sebastian Bauer, Michael A Farrell, Donncha F O'Brien, Norman Delanty, Stephanie Schorge, R Jeroen Pasterkamp, Felix Rosenow, David C Henshall
Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28279785/epigenetic-interventions-for-epileptogenesis-a-new-frontier-for-curing-epilepsy
#6
REVIEW
Iyan Younus, Doodipala Samba Reddy
This article highlights the emerging therapeutic potential of specific epigenetic modulators as promising antiepileptogenic or disease-modifying agents for curing epilepsy. Currently, there is an unmet need for antiepileptogenic agents that truly prevent the development of epilepsy in people at risk. There is strong evidence that epigenetic signaling, which exerts high fidelity regulation of gene expression, plays a crucial role in the pathophysiology of epileptogenesis and chronic epilepsy. These modifications are not hard-wired into the genome and are constantly reprogrammed by environmental influences...
March 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28235604/mir-466b-1-3p-regulates-p-glycoprotein-expression-in-rat-cerebral-microvascular-endothelial-cells
#7
Xiaobo Yang, Weimin Ren, Yiye Shao, Yinghui Chen
Epilepsy is one of the most common neurological disorders, and approximately one-third of epilepsy cases are resistant to treatment with anti-epileptic drug (AED). P-glycoprotein (P-gp) is a multi-drug transporter that is thought to play a pivotal role in multiple drug resistance (MDR) in epilepsy. The regulatory mechanism of P-gp remains largely unknown; however, recent studies have demonstrated that microRNAs (miRNAs) may regulate the chemo-resistance mediated by P-gp. This study investigated the effect of specific miRNAs that regulate P-gp expression in rat cerebral microvascular endothelial cells (RCMECs)...
February 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28104433/micrornas-in-the-pathophysiology-of-epilepsy
#8
REVIEW
Gary P Brennan, David C Henshall
Temporal lobe epilepsy is a common and often drug-resistant seizure disorder. The underlying pathological processes which give rise to the development of spontaneous seizures include neuroinflammation, cell loss, neurogenesis and dendritic abnormalities and many of these are driven by insult-induced changes in gene expression and gene expression regulation. MicroRNAs are powerful modulators of post-transcriptional gene expression which are dysregulated during epileptogenesis. The advent of locked nucleic acid (LNA) based inhibitory methods and mimic technology has facilitated in vivo functional assessment of these molecules in epilepsy...
January 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28058582/genome-wide-dna-methylation-patterns-analysis-of-noncoding-rnas-in-temporal-lobe-epilepsy-patients
#9
Wenbiao Xiao, Yuze Cao, Hongyu Long, Zhaohui Luo, Shuyu Li, Na Deng, Jianjian Wang, Xiaoyan Lu, Tianfeng Wang, Shangwei Ning, Lihua Wang, Bo Xiao
Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy and frequently evolving drug resistance. Although there is growing consensus that noncoding ribonucleic acids (ncRNAs) are modulators of TLE, the knowledge about the deoxyribonucleic acid (DNA) methylation patterns of ncRNAs in TLE remains limited. In the current study, we constructed DNA methylation profiles from 30 TLE patients and 30 healthy controls for ncRNAs, primarily focusing on long ncRNAs (lncRNAs) and microRNAs (miRNAs), by reannotating data of DNA methylation BeadChip...
January 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27926529/altered-microrna-profiles-in-plasma-exosomes-from-mesial-temporal-lobe-epilepsy-with-hippocampal-sclerosis
#10
Shaofeng Yan, Hua Zhang, Wenyan Xie, Fangang Meng, Kai Zhang, Yin Jiang, Xin Zhang, Jianguo Zhang
Mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) is the most common type of focal epilepsy. The present study aimed to explore the expression and functions of exosomal microRNAs in mTLE-HS. A total of 50 microRNAs were found to be differentially expressed in mTLE-HS compared with healthy controls. Among them, 2 were increased and 48 were decreased. The 6 significant differentially expressed candidate microRNAs (miR-3613-5p, miR-4668-5p, miR-8071, miR-197-5p, miR-4322, and miR-6781-5p ) in exosome were validated...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27852797/modulation-of-mir-146a-complement-factor-h-mediated-inflammatory-responses-in-a-rat-model-of-temporal-lobe-epilepsy
#11
Fang He, Bei Liu, Qiang Meng, Yang Sun, Weiwen Wang, Chao Wang
Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy (TLE). miRNAs represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune system homoeostasis and function. We investigated the expression and cellular distribution of miRNA-146a (miR-146a) in a rat model of TLE. Prominent up-regulation of miR-146a activation was evident in 1 week after status epilepticus (SE) and persisted in the chronic phase...
December 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27833019/changes-in-serum-mirnas-following-generalized-convulsive-seizures-in-human-mesial-temporal-lobe-epilepsy
#12
Rainer Surges, Anita Kretschmann, Khalid Abnaof, Marijke van Rikxoort, Kirsten Ridder, Holger Fröhlich, Bénédicte Danis, Rafal M Kaminski, Patrik Foerch, Christian E Elger, Frank Weinsberg, Alexander Pfeifer
MicroRNAs (miRNAs) are key regulators of gene expression and are involved in the pathomechanisms of epilepsy. MiRNAs may also serve as peripheral biomarkers of epilepsy. We investigated the miRNA profile in the blood serum of patients suffering from mesial temporal lobe epilepsy (mTLE) following a single focal seizure evolving to a bilateral convulsive seizure (BCS) during video-EEG monitoring. Data of 15 patients were included in the final analysis. MiRNA expression was determined using Real Time-PCR followed by thorough bioinformatical analysis of expression levels...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27824513/aberrant-expression-of-mir-323a-5p-in-patients-with-refractory-epilepsy-caused-by-focal-cortical-dysplasia
#13
Ningwei Che, Guo Zu, Tingting Zhou, Xiaofeng Wang, Yuqiang Sun, Zeshi Tan, Yaoling Liu, Dong Wang, Xiaodong Luo, Ze Zhao, Yue Zhang, Minghai Wei, Jian Yin
BACKGROUND: Epilepsy remains one of the most common clinical neurological disorders. About a third of patients with epilepsy are refractory to drug treatment, mainly as a result of focal cortical dysplasia (FCD). In this study, we analyzed the aberrant expression of microRNAs (miRNAs) in the cortex and plasma of FCD patients. METHODS: Cortical samples were collected from nine patients with refractory epilepsy caused by FCD who underwent surgery, and from eight volunteers (control group) undergoing emergency surgery for hypertensive cerebral hemorrhage...
January 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/27748060/developmental-regulation-of-rna-processing-by-rbfox-proteins
#14
REVIEW
John G Conboy
The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3'UTRs, and pre-miRNAs hairpin structures. Versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing...
March 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27731509/microrna-139-5p-negatively-regulates-nr2a-containing-nmda-receptor-in-the-rat-pilocarpine-model-and-patients-with-temporal-lobe-epilepsy
#15
Walid A Alsharafi, Bo Xiao, Jing Li
OBJECTIVES: Regulation of N-methyl-d-aspartate (NMDA) subunits NR2A and NR2B expression during status epilepticus (SE) remains incompletely understood. Here we explored the role of brain-enriched microRNA (miR)-139-5p in this process. METHODS: miRNA microarray was performed to examine changes in miRNA expression in the rat pilocarpine model following NMDA-receptor blockade. The dynamic expression patterns of miR-139-5p, NR2A, and NR2B levels were measured in rats during the three phases of temporal lobe epilepsy (TLE) development using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot...
November 2016: Epilepsia
https://www.readbyqxmd.com/read/27725160/increased-precursor-microrna-21-following-status-epilepticus-can-compete-with-mature-microrna-21-to-alter-translation
#16
Kayam Chak, Biswajoy Roy-Chaudhuri, Hak Kyun Kim, Kayla C Kemp, Brenda E Porter, Mark A Kay
MicroRNA-21 (miR-21) is consistently up-regulated in various neurological disorders, including epilepsy. Here, we show that the biogenesis of miR-21 is altered following pilocarpine-induced status epilepticus (SE) with an increase in precursor miR-21 (pre-miR-21) in rats. We demonstrate that pre-miR-21 has an energetically favorable site overlapping with the miR-21 binding site and competes with mature miR-21 for binding in the 3'UTR of TGFBR2 mRNA, but not NT-3 mRNA in vitro. This binding competition influences miR-21-mediated repression in vitro and correlates with the increase in TGFBR2 and decrease in NT-3 following SE...
December 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27695061/identification-of-micrornas-with-dysregulated-expression-in-status-epilepticus-induced-epileptogenesis
#17
Mykaella Andrade de Araújo, Thalita Ewellyn Batista Sales Marques, Shirley Octacílio-Silva, Carmem Lúcia de Arroxelas-Silva, Marília Gabriella Alves Goulart Pereira, José Eduardo Peixoto-Santos, Ludmyla Kandratavicius, João Pereira Leite, Norberto Garcia-Cairasco, Olagide Wagner Castro, Marcelo Duzzioni, Geraldo Aleixo Passos, Maria Luisa Paçó-Larson, Daniel Leite Góes Gitaí
The involvement of miRNA in mesial temporal lobe epilepsy (MTLE) pathogenesis has increasingly become a focus of epigenetic studies. Despite advances, the number of known miRNAs with a consistent expression response during epileptogenesis is still small. Addressing this situation requires additional miRNA profiling studies coupled to detailed individual expression analyses. Here, we perform a miRNA microarray analysis of the hippocampus of Wistar rats 24 hours after intra-hippocampal pilocarpine-induced Status Epilepticus (H-PILO SE)...
2016: PloS One
https://www.readbyqxmd.com/read/27689807/expression-of-microrna-129-2-3p-and-microrna-935-in-plasma-and-brain-tissue-of-human-refractory-epilepsy
#18
Yuqiang Sun, Xiaofeng Wang, Zeyang Wang, Yuanyang Zhang, Ningwei Che, Xiadong Luo, Zeshi Tan, Xu Sun, Xinyu Li, Kang Yang, Guanyu Wang, Lan Luan, Yaoling Liu, Xiao Zheng, Minghai Wei, Huakun Cheng, Jian Yin
OBJECTIVE: Numerous microRNAs (miRNAs) are differentially expressed in specific diseases, suggesting possible use as diagnostic or prognostic biomarkers. The purpose of this study is to investigate the expression levels of miR-129-2-3p and miR-935 in cortical brain tissue and plasma samples from controls and refractory temporal lobe epilepsy (TLE) patients to evaluate the utility of these measures as diagnostic biomarkers. METHODS: The study was divided into three phases...
September 23, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27681419/microrna-mediated-downregulation-of-the-potassium-channel-kv4-2-contributes-to-seizure-onset
#19
Christina Gross, Xiaodi Yao, Tobias Engel, Durgesh Tiwari, Lei Xing, Shane Rowley, Scott W Danielson, Kristen T Thomas, Eva M Jimenez-Mateos, Lindsay M Schroeder, Raymund Y K Pun, Steve C Danzer, David C Henshall, Gary J Bassell
Seizures are bursts of excessive synchronized neuronal activity, suggesting that mechanisms controlling brain excitability are compromised. The voltage-gated potassium channel Kv4.2, a major mediator of hyperpolarizing A-type currents in the brain, is a crucial regulator of neuronal excitability. Kv4.2 expression levels are reduced following seizures and in epilepsy, but the underlying mechanisms remain unclear. Here, we report that Kv4.2 mRNA is recruited to the RNA-induced silencing complex shortly after status epilepticus in mice and after kainic acid treatment of hippocampal neurons, coincident with reduction of Kv4...
September 27, 2016: Cell Reports
https://www.readbyqxmd.com/read/27666871/differential-expression-of-mir-184-in-temporal-lobe-epilepsy-patients-with-and-without-hippocampal-sclerosis-influence-on-microglial-function
#20
Bénédicte Danis, Marijke van Rikxoort, Anita Kretschmann, Jiong Zhang, Patrice Godard, Lidija Andonovic, Franziska Siegel, Pitt Niehusmann, Etienne Hanon, Daniel Delev, Marec von Lehe, Rafal M Kaminski, Alexander Pfeifer, Patrik Foerch
Epilepsy is one of the most common neurological disorders characterized by recurrent seizures due to neuronal hyperexcitability. Here we compared miRNA expression patterns in mesial temporal lobe epilepsy with and without hippocampal sclerosis (mTLE + HS and mTLE -HS) to investigate the regulatory mechanisms differentiating both patient groups. Whole genome miRNA sequencing in surgically resected hippocampi did not reveal obvious differences in expression profiles between the two groups of patients. However, one microRNA (miR-184) was significantly dysregulated, which was confirmed by qPCR...
September 26, 2016: Scientific Reports
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