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Epilepsy microRNA

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https://www.readbyqxmd.com/read/28808237/coding-and-small-non-coding-transcriptional-landscape-of-tuberous-sclerosis-complex-cortical-tubers-implications-for-pathophysiology-and-treatment
#1
James D Mills, Anand M Iyer, Jackelien van Scheppingen, Anika Bongaarts, Jasper J Anink, Bart Janssen, Till S Zimmer, Wim G Spliet, Peter C van Rijen, Floor E Jansen, Martha Feucht, Johannes A Hainfellner, Pavel Krsek, Josef Zamecnik, Katarzyna Kotulska, Sergiusz Jozwiak, Anna Jansen, Lieven Lagae, Paolo Curatolo, David J Kwiatkowski, R Jeroen Pasterkamp, Ketharini Senthilkumar, Lars von Oerthel, Marco F Hoekman, Jan A Gorter, Peter B Crino, Angelika Mühlebner, Brendon P Scicluna, Eleonora Aronica
Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). TSC is associated with autism, intellectual disability and severe epilepsy. Cortical tubers are believed to represent the neuropathological substrates of these disabling manifestations in TSC. In the presented study we used high-throughput RNA sequencing in combination with systems-based computational approaches to investigate the complexity of the TSC molecular network...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676013/the-challenge-of-microrna-as-a-biomarker-of-epilepsy
#2
Yihong Ma
Epilepsy is one of chronic severe neurological disorders possess to recurring seizures which product abnormal and synchronous in the brain neurons other characteristic is including upregulate mortality rate, and decreased social participation and quality of life. Epilepsy as well as ictogenesis included treatments. But anti-epileptic drugs are only effective in less than one third of epilepsy patients, and biomarkers predicting are not available when the specific antiepileptic drugs treated. Advanced studies have showed that miRNA may be a key in the pathogenesis of epilepsy beginning in the early 2000 years...
July 3, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28607431/cerebrospinal-fluid-micrornas-are-potential-biomarkers-of-temporal-lobe-epilepsy-and-status-epilepticus
#3
Rana Raoof, Eva M Jimenez-Mateos, Sebastian Bauer, Björn Tackenberg, Felix Rosenow, Johannes Lang, Müjgan Dogan Onugoren, Hajo Hamer, Tessa Huchtemann, Peter Körtvélyessy, Niamh M C Connolly, Shona Pfeiffer, Jochen H M Prehn, Michael A Farrell, Donncha F O'Brien, David C Henshall, Catherine Mooney
There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28587680/in-vitro-antineoplastic-effects-of-brivaracetam-and-lacosamide-on-human-glioma-cells
#4
Ambra Rizzo, Sara Donzelli, Vita Girgenti, Andrea Sacconi, Chiara Vasco, Andrea Salmaggi, Giovanni Blandino, Marta Maschio, Emilio Ciusani
BACKGROUND: Epilepsy is a frequent symptom in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patients are not uncommon. Multidrug resistance proteins (MRPs) and P-gp are over-represented in brain tissue of patients with drug-resistant epilepsy, suggesting their involvement in the clearance of antiepileptic medications. In addition to their anticonvulsant action, some drugs have been documented for cytotoxic effects...
June 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28584127/dynamic-changes-in-murine-forebrain-mir-211-expression-associate-with-cholinergic-imbalances-and-epileptiform-activity
#5
Uriya Bekenstein, Nibha Mishra, Dan Z Milikovsky, Geula Hanin, Daniel Zelig, Liron Sheintuch, Amit Berson, David S Greenberg, Alon Friedman, Hermona Soreq
Epilepsy is a common neurological disease, manifested in unprovoked recurrent seizures. Epileptogenesis may develop due to genetic or pharmacological origins or following injury, but it remains unclear how the unaffected brain escapes this susceptibility to seizures. Here, we report that dynamic changes in forebrain microRNA (miR)-211 in the mouse brain shift the threshold for spontaneous and pharmacologically induced seizures alongside changes in the cholinergic pathway genes, implicating this miR in the avoidance of seizures...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28562528/microrna-profiling-in-the-dentate-gyrus-in-epileptic-rats-the-role-of-mir-187-3p
#6
Suya Zhang, Yubin Kou, Chunmei Hu, Yan Han
This study aimed to explore the role of aberrant miRNA expression in epilepsy and to identify more potential genes associated with epileptogenesis.The miRNA expression profile of GSE49850, which included 20 samples from the rat epileptic dentate gyrus at 7, 14, 30, and 90 days after electrical stimulation and 20 additional samples from sham time-matched controls, was downloaded from the Gene Expression Omnibus database. The significantly differentially expressed miRNAs were identified in stimulated samples at each time point compared to time-matched controls, respectively...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28528202/microrna-129-5p-inhibits-the-development-of-autoimmune-encephalomyelitis-related-epilepsy-by-targeting-hmgb1-through-the-tlr4-nf-kb-signaling-pathway
#7
Ai-Hua Liu, Ya-Ting Wu, Yu-Ping Wang
The study aimed to explore the effects of microRNA-129-5p (miR-129-5p) on the development of autoimmune encephalomyelitis (AE)-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway in a rat model. AE-related epilepsy models were established. Sprague-Dawley (SD) rats were randomly divided into control, model, miR-129-5p mimics, miR-129-5p inhibitor, HMGB1 shRNA, TLR4/NF-kB (TLR4/NF-kB signaling pathway was inhibited) and miR-129-5p mimics+HMGB1 shRNA groups respectively. Latency to a first epilepsy seizure attack was recorded...
June 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28496112/-tornado-theranostic-one-step-rna-detector-microfluidic-disc-for-the-direct-detection-of-microrna-134-in-plasma-and-cerebrospinal-fluid
#8
Hazel McArdle, Eva M Jimenez-Mateos, Rana Raoof, Eadaoin Carthy, David Boyle, Hany ElNaggar, Norman Delanty, Hajo Hamer, Muejgdan Dogan, Tessa Huchtemann, Peter Kӧrtvelyessy, Felix Rosenow, Robert J Forster, David C Henshall, Elaine Spain
Diagnosis of seizure disorders such as epilepsy currently relies on clinical examination and electroencephalogram recordings and is associated with substantial mis-diagnosis. The miRNA, miR-134 (MIR134 in humans), has been found to be elevated in brain tissue after experimental status epilepticus and in human epilepsy cells and their detection in biofluids may serve as unique biomarkers. miRNAs from unprocessed human plasma and human cerebrospinal fluid samples were used in a novel electrochemical detection based on electrocatalytic platinum nanoparticles inside a centrifugal microfluidic device where the sandwich assay is formed using an event triggered release system, suitable for the rapid point-of-care detection of low abundance biomarkers of disease...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28487411/a-microrna-129-5p-rbfox-crosstalk-coordinates-homeostatic-downscaling-of-excitatory-synapses
#9
Marek Rajman, Franziska Metge, Roberto Fiore, Sharof Khudayberdiev, Ayla Aksoy-Aksel, Silvia Bicker, Cristina Ruedell Reschke, Rana Raoof, Gary P Brennan, Norman Delanty, Michael A Farrell, Donncha F O'Brien, Sebastian Bauer, Braxton Norwood, Morten T Veno, Marcus Krüger, Thomas Braun, Jørgen Kjems, Felix Rosenow, David C Henshall, Christoph Dieterich, Gerhard Schratt
Synaptic downscaling is a homeostatic mechanism that allows neurons to reduce firing rates during chronically elevated network activity. Although synaptic downscaling is important in neural circuit development and epilepsy, the underlying mechanisms are poorly described. We performed small RNA profiling in picrotoxin (PTX)-treated hippocampal neurons, a model of synaptic downscaling. Thereby, we identified eight microRNAs (miRNAs) that were increased in response to PTX, including miR-129-5p, whose inhibition blocked synaptic downscaling in vitro and reduced epileptic seizure severity in vivo Using transcriptome, proteome, and bioinformatic analysis, we identified the calcium pump Atp2b4 and doublecortin (Dcx) as miR-129-5p targets...
June 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28384161/microrna-hsa-mir-134-is-a-circulating-biomarker-for-mesial-temporal-lobe-epilepsy
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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