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Epilepsy microRNA

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...
October 17, 2016: Wiley Interdisciplinary Reviews. RNA
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...
October 12, 2016: Epilepsia
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 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...
October 7, 2016: Experimental Neurology
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
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
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
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
Daniel T Hass, Colin J Barnstable
Reactive oxygen species (ROS) are free radicals thought to mediate the neurotoxic effects of several neurodegenerative disorders. In the central nervous system, ROS can also trigger a phenotypic switch in both astrocytes and microglia that further aggravates neurodegeneration, termed reactive gliosis. Negative regulators of ROS, such as mitochondrial uncoupling protein 2 (UCP2) are neuroprotective factors that decrease neuron loss in models of stroke, epilepsy, and parkinsonism. However, it is unclear whether UCP2 acts purely to prevent ROS production, or also to prevent gliosis...
August 2016: Neural Regeneration Research
Jinxian Yuan, Hao Huang, Xin Zhou, Xi Liu, Shu Ou, Tao Xu, Ruohan Li, Limin Ma, Yangmei Chen
Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (miR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether miR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model...
2016: Neural Plasticity
Klara Piletič, Tanja Kunej
MicroRNAs (miRNAs) are short non-coding RNAs that act as important regulators of gene expression as part of the epigenetic machinery. In addition to posttranscriptional gene silencing by miRNAs, the epigenetic mechanisms also include DNA methylation, histone modifications and their crosstalk. Epigenetic modifications were reported to play an important role in many disease onsets and progressions and can be used to explain several features of complex diseases, such as late onset and fluctuation of symptoms. However, miRNAs not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation and histone modification like any other protein-coding gene...
October 2016: Archives of Toxicology
Yaohua Li, Cheng Huang, Peimin Feng, Yanping Jiang, Wei Wang, Dong Zhou, Lei Chen
Evidence suggest that overexpression of hypoxia-inducible factor-1α (HIF-1α) is linked to multidrug resistance of epilepsy. Here we explored whether aberrant expression of HIF-1α is regulated by miRNAs. Genome-wide microRNA expression profiling was performed on temporal cortex resected from mesial temporal lobe epilepsy (mTLE) patients and age-matched controls. miRNAs that are putative regulator of HIF-1α were predicted via target scan and confirmed by real-time quantitative polymerase chain reaction (RT-qPCR)...
2016: Scientific Reports
Marijn Schouten, Pascal Bielefeld, Silvina A Fratantoni, Chantal J Hubens, Sander R Piersma, Thang V Pham, Rob A Voskuyl, Paul J Lucassen, Connie R Jimenez, Carlos P Fitzsimons
Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons. Here we explored these early phenotypical changes in the DG 3 days after a systemic injection of KA inducing status epilepticus (KA-SE), in mice...
2016: Scientific Data
Yang Yuan, Wang Xiang, Liu Yanhui, Liang Ruofei, Mao Yunhe, Luo Jiewen, Mao Qing
OBJECTIVE: Approximately 80% of glioma patients will experience at least one seizure activity during the course of the disease, and because the etiology of glioma-related seizure is most likely multifactorial and complex, it remains poorly understood. MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators. MicroRNA-128 was found to be decreased in glioblastoma, and knockout of the microRNA-128a gene could induce epilepsy in mice. Based on the Chinese Glioma Genome Atlas and previous study, we hypothesized that dysregulation of miR-128 expression may play a role in the pathogenesis of TAE in low-grade glioma...
August 11, 2016: Epilepsy Research
K Melodi McSweeney, Ayal B Gussow, Shelton S Bradrick, Sarah A Dugger, Sahar Gelfman, Quanli Wang, Slavé Petrovski, Wayne N Frankel, Michael J Boland, David B Goldstein
Cultured neuronal networks monitored with microelectrode arrays (MEAs) have been used widely to evaluate pharmaceutical compounds for potential neurotoxic effects. A newer application of MEAs has been in the development of in vitro models of neurological disease. Here, we directly evaluated the utility of MEAs to recapitulate in vivo phenotypes of mature microRNA-128 (miR-128) deficiency, which causes fatal seizures in mice. We show that inhibition of miR-128 results in significantly increased neuronal activity in cultured neuronal networks derived from primary mouse cortical neurons...
October 2016: Genome Research
Tian Li, Yaoyun Kuang, Bin Li
BACKGROUND: mRNA expression in a cell or subcellular organelle is precisely regulated for the purpose of gene function regulation. The 3' untranslated region (3'UTR) of mRNA is the binding target of microRNA and RNA binding proteins. Their interactions regulate mRNA level in specific subcellular regions and determine the intensity of gene repression. The mutations in the coding region of voltage-gated sodium channel alpha 1 subunit gene, SCN1A, were identified in epileptic patients and confirmed as causative factors of epilepsy...
2016: BMC Genetics
Licheng Chen, Hao Zheng, Shimeng Zhang
Epilepsy is a common type of neurological disorder with complex etiology. The mechanisms are still not clear. MicroRNAs are endogenous noncoding RNAs with many physiological activities. Multiple microRNAs were abnormally expressed in status epilepticus, including miR-210. In this study, we applied lithium chloride and pilocarpine to induce epileptic activity and aimed to disclose the potential mechanisms. Our data showed that miR-210 was significantly upregulated in hippocampus one day after modeling (P<0...
2016: Neuropsychiatric Disease and Treatment
Yuhan Liao, Yiqing Huang, Xixia Liu, Chun Luo, Donghua Zou, Xing Wei, Qi Huang, Yuan Wu
The down-regulation of microRNA-328a (miR-328a) in pentylenetetrazole (PTZ)-kindled rats with memory impairment was demonstrated in our previous study, while any contribution of miR-328a to cognitive dysfunction of PTZ-kindled rats remains unknown. In this study we have investigated the effect and the underlying mechanism of miR-328a on the cognitive function in PTZ-kindled rats. 48 SD male rats were divided into 4 groups as follows: a PTZ kindled group, a miR-328a antagomir group, an antagomir-control group, and a sham group (n=12 for each)...
July 2016: Brain Research Bulletin
Naim Panjwani, Michael D Wilson, Laura Addis, Jennifer Crosbie, Elaine Wirrell, Stéphane Auvin, Roberto H Caraballo, Maria Kinali, David McCormick, Caroline Oren, Jacqueline Taylor, John Trounce, Tara Clarke, Cigdem I Akman, Steven L Kugler, David E Mandelbaum, Patricia McGoldrick, Steven M Wolf, Paul Arnold, Russell Schachar, Deb K Pal, Lisa J Strug
OBJECTIVE: Rolandic epilepsy is a common genetic focal epilepsy of childhood characterized by centrotemporal sharp waves on electroencephalogram. In previous genome-wide analysis, we had reported linkage of centrotemporal sharp waves to chromosome 11p13, and fine mapping with 44 SNPs identified the ELP4-PAX6 locus in two independent US and Canadian case-control samples. Here, we aimed to find a causative variant for centrotemporal sharp waves using a larger sample and higher resolution genotyping array...
July 2016: Annals of Clinical and Translational Neurology
Yang Li, Jinqiu Wang, Chunming Jiang, Guo Zheng, Xiaopeng Lu, Hu Guo
PURPOSE: MicroRNA (miRNA), functions as gene regulators, plays crucial roles in pathogenesis of epilepsy. We hypothesized that single nucleotide polymorphisms (SNPs) in miRNA may be associated with childhood epilepsy. METHOD: We first genotyped the selected four SNPs (miR-146a rs57095329, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444) in 267 paired childhood epilepsy patients and controls using the TaqMan assay, and evaluated the associations of the four SNPs with the risk of epilepsy...
August 2016: Seizure: the Journal of the British Epilepsy Association
Zhengxu Cai, Song Li, Sheng Li, Fan Song, Zhen Zhang, Guanhua Qi, Tianbai Li, Juanjuan Qiu, Jiajia Wan, Hua Sui, Huishu Guo
Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155) could serve as a promising treatment of mesial temporal lobe epilepsy. In the current study, the therapeutic potential of miR-155 antagonist against temporal lobe epilepsy (TLE) was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG) recordings...
2016: Frontiers in Pharmacology
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