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Chromatin epilepsy

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https://www.readbyqxmd.com/read/29407793/promoter-analysis-and-transcriptional-regulation-of-human-carbonic-anhydrase-viii-gene-in-a-merrf-disease-cell-model
#1
Che-Min Lo, Yi-Shing Ma, Yau-Huei Wei, Benjamin Y T Hsieh, Mingli Hsieh
Myoclonic epilepsy with ragged-red fibers (MERRF) is a maternally inherited mitochondrial neuromuscular disease. We previously reported a significant decrease of mRNA and protein levels of nuclear DNA-encoded carbonic anhydrase VIII (CA8) in MERRF cybrids harboring A8344G mutation in mitochondrial DNA (mtDNA). In this study, we established a reporter construct of luciferase gene-carrying hCA8 promoter containing several putative transcription factor-binding sites, including GC-box, AP-2 and TATA-binding element in the 5'flanking region of the hCA8 gene...
March 1, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29288635/foxd3-inhibits-scn2a-gene-transcription-in-intractable-epilepsy-cell-models
#2
Jun Xiang, Fang Wen, Lingyun Zhang, Yu Zhou
The expression of sodium voltage-gated channel alpha subunit 2 (SCN2A) is closely related to the development of epilepsy. This study investigated regulatory element of the SCN2A gene involved in epilepsy. An intractable epilepsy cell model was constructed using hippocampal primary neurons and the SH-SY5Y cell line. SCN2A protein and gene expression in cells as well as the level of lactic acid dehydrogenase (LDH) in the cell culture supernatants was detected. Potential regulatory factors of SCN2A and its upstream regulatory elements were identified using the dual-luciferase reporter assay...
April 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29277263/genetics-of-human-epilepsies-continuing-progress
#3
Pierre Szepetowski
Numerous epilepsy genes have been identified in the last years, mostly in the (rare) monogenic forms and thanks to the increased availability and the decreased cost of next-generation sequencing approaches. Besides the somehow expected group of epilepsy genes encoding various ion channel subunits (e.g. sodium or potassium channel subunits, or GABA receptors, or glutamate-gated NMDA receptors), more diversity has emerged recently, with novel epilepsy genes encoding proteins playing a wide range of physiological roles at the cellular and molecular levels, such as synaptic proteins, members of the mTOR pathway, or proteins involved in chromatin remodeling...
December 22, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29248671/chromatin-in-nervous-system-development-and-disease
#4
EDITORIAL
Shigeki Iwase, Donna M Martin
Epigenetic regulation of gene expression is critical during development of the central nervous system. Pathogenic variants in genes encoding epigenetic factors have been found to cause a wide variety of neurodevelopmental disorders including Autism spectrum disorder, intellectual disability, and epilepsy. Cancers affecting neuronal and glial cells in the brain have also been shown to exhibit somatic mutations in epigenetic regulators, suggesting chromatin-based links between regulated and dysregulated cellular proliferation and differentiation...
March 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29229852/regulatory-networks-specifying-cortical-interneurons-from-human-embryonic-stem-cells-reveal-roles-for-chd2-in-interneuron-development
#5
Kesavan Meganathan, Emily M A Lewis, Paul Gontarz, Shaopeng Liu, Edouard G Stanley, Andrew G Elefanty, James E Huettner, Bo Zhang, Kristen L Kroll
Cortical interneurons (cINs) modulate excitatory neuronal activity by providing local inhibition. During fetal development, several cIN subtypes derive from the medial ganglionic eminence (MGE), a transient ventral telencephalic structure. While altered cIN development contributes to neurodevelopmental disorders, the inaccessibility of human fetal brain tissue during development has hampered efforts to define molecular networks controlling this process. Here, we modified protocols for directed differentiation of human embryonic stem cells, obtaining efficient, accelerated production of MGE-like progenitors and MGE-derived cIN subtypes with the expected electrophysiological properties...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29213033/-epigenetic-modifications-of-chromatin-in-epilepsy-a-potential-mechanism-of-pharmacoresistance
#6
L S Sokhranyaeva, V A Aniol, N V Gulyaeva
Pharmacoresistance in epilepsy is an important problem from both clinical and fundamental perspectives. The existent hypotheses of pharmacoresistance are based on long term plastic rebuilding of the epileptic brain. One of potential mechanisms mediating such protracted changes are alterations of gene expression induced by epigenetic modifications of chromatin in brain cells of epileptic patients. Recently, changes in DNA methylation and histone post-translational modifications were reported in brain tissues of patients with pharmacoresistant epilepsy...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29187863/smooth-an-hnrnp-l-homolog-might-decrease-mitochondrial-metabolism-by-post-transcriptional-regulation-of-isocitrate-dehydrogenase-idh-and-other-metabolic-genes-in-the-sub-acute-phase-of-traumatic-brain-injury
#7
Arko Sen, Katherine Gurdziel, Jenney Liu, Wen Qu, Oluwademi O Nuga, Rayanne B Burl, Maik Hüttemann, Roger Pique-Regi, Douglas M Ruden
Traumatic brain injury (TBI) can cause persistent pathological alteration of neurons. This may lead to cognitive dysfunction, depression and increased susceptibility to life threatening diseases, such as epilepsy and Alzheimer's disease. To investigate the underlying genetic and molecular basis of TBI, we subjected w 1118 Drosophila melanogaster to mild closed head trauma and found that mitochondrial activity is reduced in the brains of these flies 24 h after inflicting trauma. To determine the transcriptomic changes after mild TBI, we collected fly heads 24 h after inflicting trauma, and performed RNA-seq analyses...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29146047/maternal-immune-activation-delays-excitatory-to-inhibitory-gamma-aminobutyric-acid-switch-in-offspring
#8
Irene Corradini, Elisa Focchi, Marco Rasile, Raffaella Morini, Genni Desiato, Romana Tomasoni, Michela Lizier, Elsa Ghirardini, Riccardo Fesce, Diego Morone, Isabella Barajon, Flavia Antonucci, Davide Pozzi, Michela Matteoli
BACKGROUND: The association between maternal infection and neurodevelopmental defects in progeny is well established, although the biological mechanisms and the pathogenic trajectories involved have not been defined. METHODS: Pregnant dams were injected intraperitoneally at gestational day 9 with polyinosinic:polycytidylic acid. Neuronal development was assessed by means of electrophysiological, optical, and biochemical analyses. RESULTS: Prenatal exposure to polyinosinic:polycytidylic acid causes an imbalanced expression of the Na+-K+-2Cl- cotransporter 1 and the K+-Cl- cotransporter 2 (KCC2)...
November 14, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29115470/dimethylation-of-histone-3-lysine-9-is-sensitive-to-the-epileptic-activity-and-affects-the-transcriptional-regulation-of-the-potassium-channel-kcnj10-gene-in-epileptic-rats
#9
Shao-Ping Zhang, Man Zhang, Hong Tao, Yan Luo, Tao He, Chun-Hui Wang, Xiao-Cheng Li, Ling Chen, Lin-Na Zhang, Tao Sun, Qi-Kuan Hu
Potassium channels can be affected by epileptic seizures and serve a crucial role in the pathophysiology of epilepsy. Dimethylation of histone 3 lysine 9 (H3K9me2) and its enzyme euchromatic histone‑lysine N‑methyltransferase 2 (G9a) are the major epigenetic modulators and are associated with gene silencing. Insight into whether H3K9me2 and G9a can respond to epileptic seizures and regulate expression of genes encoding potassium channels is the main purpose of the present study. A total of 16 subtypes of potassium channel genes in pilocarpine‑modelled epileptic rats were screened by reverse transcription‑quantitative polymerase chain reaction, and it was determined that the expression ATP‑sensitive inward rectifier potassium channel 10 (Kcnj10) increased in hippocampus and insular cortex, while the expression of most of the other subtypes decreased...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29089052/epigenetic-control-of-epilepsy-target-genes-contributes-to-a-cellular-memory-of-epileptogenesis-in-cultured-rat-hippocampal-neurons
#10
K Kiese, J Jablonski, J Hackenbracht, J K Wrosch, T W Groemer, J Kornhuber, I Blümcke, K Kobow
Hypersynchronous neuronal excitation manifests clinically as seizure (ictogenesis), and may recur spontaneously and repetitively after a variable latency period (epileptogenesis). Despite tremendous research efforts to describe molecular pathways and signatures of epileptogenesis, molecular pathomechanisms leading to chronic epilepsy remain to be clarified. We hypothesized that epigenetic modifications may form the basis for a cellular memory of epileptogenesis, and used a primary neuronal cell culture model of the rat hippocampus to study the translation of massive neuronal excitation into persisting changes of epigenetic signatures and pro-epileptogenic target gene expression...
October 31, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29076408/role-of-histone-deacetylases-hdacs-in-epilepsy-and-epileptogenesis
#11
Rita Citraro, Antonio Leo, Matteo Santoro, Giuseppe D'agostino, Andrew Constanti, Emilio Russo
BACKGROUND: Emerging evidence suggests that epigenetic mechanisms are involved in different brain functions such as the development of the nervous system and normal neuronal function. At the same time, it has been proposed that several neurological diseases are in part, caused by aberrant epigenetic modifications. Nevertheless, the mechanisms underlying pathological alterations in the brain genome are not completely understood. METHODS AND RESULTS: Post-transcriptional histone acetylation is a major mechanism of chromatin remodeling, contributing to epigenetic regulation of gene transcription...
2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28863321/the-role-of-necroptosis-in-status-epilepticus-induced-brain-injury-in-juvenile-rats
#12
Qianyun Cai, Jing Gan, Rong Luo, Yi Qu, Shiping Li, Chaomin Wan, Dezhi Mu
PURPOSE: To study the role of necroptosis in status epilepticus (SE)-induced injury in the developing brain and the possible associations of necroptosis with epileptogenesis and cognitive dysfunction. METHODS: The lithium-pilocarpine epilepsy model was reproduced in male rats at postnatal day 25. Propidium iodide (PI) staining was used to detect cell death after SE. Transmission electron microscopy (TEM) was performed to observe morphological changes in injured neurons...
October 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28841245/marked-accumulation-of-oligodendroglia-like-cells-in-temporal-lobe-epilepsy-with-amygdala-enlargement-and-hippocampal-sclerosis
#13
Daichi Sone, Masako Ikemura, Yuko Saito, Go Taniguchi, Naoto Kunii
Although an increasing number of cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have been reported, there are few pathological reports, and no clear consensus has been established. Oligodendroglia or oligodendroglia-like cells (OLCs) have recently attracted attention in epilepsy studies. Here, we report the clinical and pathological findings of a 40-year-old male TLE patient with AE and hippocampal sclerosis, in whom histopathological study demonstrated remarkable clustering of OLCs around the uncus...
August 25, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28587927/the-%C3%AE-4-subunit-of-the-voltage-gated-calcium-channel-cacnb4-regulates-the-rate-of-cell-proliferation-in-chinese-hamster-ovary-cells
#14
Mohamad Rima, Marwa Daghsni, Stephan De Waard, Nathalie Gaborit, Ziad Fajloun, Michel Ronjat, Yasuo Mori, Juan L Brusés, Michel De Waard
The β subunits of Voltage-Gated Calcium Channel (VGCC) are cytosolic proteins that interact with the VGCC pore -forming subunit and participate in the trafficking of the channel to the cell membrane and in ion influx regulation. β subunits also exert functions independently of their binding to VGCC by translocation to the cell nucleus including the control of gene expression. Mutations of the neuronal Cacnb4 (β4 ) subunit are linked to human neuropsychiatric disorders including epilepsy and intellectual disabilities...
August 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28549975/knockdown-of-epigenetic-transcriptional-co-regulator-brd2a-disrupts-apoptosis-and-proper-formation-of-hindbrain-and-midbrain-hindbrain-boundary-mhb-region-in-zebrafish
#15
Tami Murphy, Heather Melville, Eliza Fradkin, Giana Bistany, Gregory Branigan, Kelly Olsen, Catharine R Comstock, Hayley Hanby, Ellie Garbade, Angela J DiBenedetto
Brd2 is a member of the bromodomain-extraterminal domain (BET) family of proteins and functions as an acetyl-histone-directed transcriptional co-regulator and recruitment scaffold in chromatin modification complexes affecting signal-dependent transcription. While Brd2 acts as a protooncogene in mammalian blood, developmental studies link it to regulation of neuronal apoptosis and epilepsy, and complete knockout of the gene is invariably embryonic lethal. In Drosophila, the Brd2 homolog acts as a maternal effect factor necessary for segment formation and identity and proper expression of homeotic loci, including Ultrabithorax and engrailed...
August 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28403881/glucocorticoid-receptor-represses-brain-derived-neurotrophic-factor-expression-in-neuron-like-cells
#16
Hui Chen, Marc Lombès, Damien Le Menuet
Brain-derived neurotrophic factor (BDNF) is involved in many functions such as neuronal growth, survival, synaptic plasticity and memorization. Altered expression levels are associated with many pathological situations such as depression, epilepsy, Alzheimer's, Huntington's and Parkinson's diseases. Glucocorticoid receptor (GR) is also crucial for neuron functions, via binding of glucocorticoid hormones (GCs). GR actions largely overlap those of BDNF. It has been proposed that GR could be a regulator of BDNF expression, however the molecular mechanisms involved have not been clearly defined yet...
April 12, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28275159/enduring-memory-impairments-provoked-by-developmental-febrile-seizures-are-mediated-by-functional-and-structural-effects-of-neuronal-restrictive-silencing-factor
#17
Katelin P Patterson, Jeremy M Barry, Megan M Curran, Akanksha Singh-Taylor, Gary Brennan, Neggy Rismanchi, Matias Page, Yoav Noam, Gregory L Holmes, Tallie Z Baram
In a subset of children experiencing prolonged febrile seizures (FSs), the most common type of childhood seizures, cognitive outcomes are compromised. However, the underlying mechanisms are unknown. Here we identified significant, enduring spatial memory problems in male rats following experimental prolonged FS (febrile status epilepticus; eFSE). Remarkably, these deficits were abolished by transient, post hoc interference with the chromatin binding of the transcriptional repressor neuron restrictive silencing factor (NRSF or REST)...
April 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28212175/advances-in-epilepsy-gene-discovery-and-implications-for-epilepsy-diagnosis-and-treatment
#18
Joseph D Symonds, Sameer M Zuberi, Michael R Johnson
PURPOSE OF REVIEW: Epilepsy genetics is shifting from the academic pursuit of gene discovery to a clinical discipline based on molecular diagnosis and stratified medicine. We consider the latest developments in epilepsy genetics and review how gene discovery in epilepsy is influencing the clinical classification of epilepsy and informing new therapeutic approaches and drug discovery. RECENT FINDINGS: Recent studies highlighting the importance of mutation in GABA receptors, NMDA receptors, potassium channels, G-protein coupled receptors, mammalian target of rapamycin pathway and chromatin remodeling are discussed...
April 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28197553/the-role-of-sirt1-in-epileptogenesis
#19
Alicia M Hall, Gary P Brennan, Tiffany M Nguyen, Akanksha Singh-Taylor, Hyun-Seung Mun, Mary J Sargious, Tallie Z Baram
The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults, including trauma, stroke, tumors, infections, and long seizures [status epilepticus (SE)], create a neuronal state of increased metabolic demand or decreased energy supply. Neurons express molecules that monitor their metabolic state, including sirtuins (Sirts). Sirtuins deacetylate cytoplasmic proteins and nuclear histones, and their epigenetic modulation of the chromatin governs the expression of many genes, influencing neuronal properties...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28111355/epigenetics-in-epilepsy
#20
REVIEW
K Kobow, I Blümcke
Approximately 50 million people have epilepsy, making it the most common chronic and severe neurological disease worldwide, with increased risk of mortality and psychological and socioeconomic consequences impairing quality of life. More than 30% of patients with epilepsy have inadequate control of their seizures with drug therapy. Any structural brain lesion can provoke epilepsy. However, progression of seizure activity as well as the development of drug-resistance remains difficult to predict, irrespective of the underlying epileptogenic condition, i...
February 22, 2018: Neuroscience Letters
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