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epilepsy mouse model

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https://www.readbyqxmd.com/read/29035369/epigenetic-suppression-of-hippocampal-calbindin-d28k-by-%C3%AE-fosb-drives-seizure-related-cognitive-deficits
#1
Jason C You, Kavitha Muralidharan, Jin W Park, Iraklis Petrof, Mark S Pyfer, Brian F Corbett, John J LaFrancois, Yi Zheng, Xiaohong Zhang, Carrie A Mohila, Daniel Yoshor, Robert A Rissman, Eric J Nestler, Helen E Scharfman, Jeannie Chin
The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer's disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood...
October 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29024712/brief-activation-of-gabaergic-interneurons-initiates-the-transition-to-ictal-events-through-post-inhibitory-rebound-excitation
#2
Michael Chang, Joshua A Dian, Suzie Dufour, Lihua Wang, Homeira Moradi-Chameh, Meera Ramani, Liang Zhang, Peter L Carlen, Thilo Womelsdorf, Taufik A Valiante
Activation of γ-aminobutyric acid (GABAA) receptors have been associated with the onset of epileptiform events. To investigate if a causal relationship exists between GABAA receptor activation and ictal event onset, we activated inhibitory GABAergic networks in the superficial layer (2/3) of the somatosensory cortex during hyperexcitable conditions using optogenetic techniques in mice expressing channelrhodopsin-2 in all GABAergic interneurons. We found that a brief 30ms light pulse reliably triggered either an interictal-like event (IIE) or ictal-like ("ictal") event in the in vitro cortical 4-Aminopyridine (4-AP) slice model...
October 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29023667/postnatal-reduction-of-tuberous-sclerosis-complex-1-expression-in-astrocytes-and-neurons-causes-seizures-in-an-age-dependent-manner
#3
Jia Zou, Bo Zhang, David H Gutmann, Michael Wong
OBJECTIVE: Epilepsy is one of the most prominent symptoms of tuberous sclerosis complex (TSC), a genetic disorder, and may be related to developmental defects resulting from impaired TSC1 or TSC2 gene function in astrocytes and neurons. Inactivation of the Tsc1 gene driven by a glial-fibrillary acidic protein (GFAP) promoter during embryonic brain development leads to widespread pathologic effects on astrocytes and neurons, culminating in severe, progressive epilepsy in mice (Tsc1(GFAP)(-Cre) mice)...
October 12, 2017: Epilepsia
https://www.readbyqxmd.com/read/29019056/physical-exercise-modulates-l-dopa-regulated-molecular-pathways-in-the-mptp-mouse-model-of-parkinson-s-disease
#4
Cornelius J H M Klemann, Helena Xicoy, Geert Poelmans, Bas R Bloem, Gerard J M Martens, Jasper E Visser
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas...
October 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29017573/gad67-haploinsufficiency-reduces-amyloid-pathology-and-rescues-olfactory-memory-deficits-in-a-mouse-model-of-alzheimer-s-disease
#5
Yue Wang, Zheng Wu, Yu-Ting Bai, Gang-Yi Wu, Gong Chen
BACKGROUND: Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, affecting millions of people worldwide. Although dysfunction of multiple neurotransmitter systems including cholinergic, glutamatergic and GABAergic systems has been associated with AD progression the underlying mechanisms remain elusive. We and others have recently found that GABA content is elevated in AD brains and linked to cognitive deficits in AD mouse models. The glutamic acid decarboxylase 67 (GAD67) is the major enzyme converting glutamate into GABA and has been implied in a number of neurological disorders such as epilepsy and schizophrenia...
October 10, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28990289/valproate-plays-a-protective-role-against-migraine-by-inhibiting-protein-kinase-c-signalling-in-nitroglycerin-treated-mice
#6
Lian Yi, Qiong Wu, Nan Chen, Ge Song, Chao Wang, Qiaoge Zou, Zhongling Zhang
Migraine is a common disease with a high morbidity. Valproate (VP) is used as an anti-epilepsy drug in clinic. This study aimed to investigate the role of VP in nitroglycerin (NTG)-induced migraine using a mouse model. NTG was employed by intraperitoneal injection to induce a migraine model in mice. The NTG administration caused mouse head discomforts, decreased tolerance to cold or hot stimulation and increased content of nitric oxide (NO), calcitonin gene related peptide (CGRP) and Neuropeptide Y (NPY) in serum, which were ameliorated by intraperitoneal injection of VP...
October 8, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28974734/knockout-of-the-epilepsy-gene-depdc5-in-mice-causes-severe-embryonic-dysmorphology-with-hyperactivity-of-mtorc1-signalling
#7
James Hughes, Ruby Dawson, Melinda Tea, Dale McAninch, Sandra Piltz, Dominique Jackson, Laura Stewart, Michael G Ricos, Leanne M Dibbens, Natasha L Harvey, Paul Thomas
DEPDC5 mutations have recently been shown to cause epilepsy in humans. Evidence from in vitro studies has implicated DEPDC5 as a negative regulator of mTORC1 during amino acid insufficiency as part of the GATOR1 complex. To investigate the role of DEPDC5 in vivo we generated a null mouse model using targeted CRISPR mutagenesis. Depdc5 homozygotes display severe phenotypic defects between 12.5-15.5 dpc, including hypotrophy, anaemia, oedema, and cranial dysmorphology as well as blood and lymphatic vascular defects...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28973916/cannabidiol-attenuates-seizures-and-social-deficits-in-a-mouse-model-of-dravet-syndrome
#8
Joshua S Kaplan, Nephi Stella, William A Catterall, Ruth E Westenbroek
Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel NaV1.1. The duration and severity of thermally induced seizures and the frequency of spontaneous seizures were substantially decreased...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28968899/cntnap4-impacts-epilepsy-through-gabaa-receptors-regulation-evidence-from-temporal-lobe-epilepsy-patients-and-mouse-models
#9
Yafei Shangguan, Xin Xu, Baigalimaa Ganbat, Yun Li, Wei Wang, Yong Yang, Xi Lu, Chao Du, Xin Tian, Xuefeng Wang
Epilepsy is a serious neurological condition characterized by recurrent unprovoked seizures. The exact etiology of epilepsy is not fully understood. Here, we demonstrated that the expression of contactin-associated protein-like 4 (CNTNAP4) was decreased in the temporal neocortex of epileptic patients and in the hippocampus and cortex of epileptic mice. Lentivirus-mediated knock-down of CNTNAP4 in the hippocampus increased mice susceptibility to epilepsy. Conversely, lentivirus-mediated overexpression of CNTNAP4 decreased epileptic behavior in mice...
August 22, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28939854/a-combination-of-nmda-and-ampa-receptor-antagonists-retards-granule-cell-dispersion-and-epileptogenesis-in-a-model-of-acquired-epilepsy
#10
Alina Schidlitzki, Friederike Twele, Rebecca Klee, Inken Waltl, Kerstin Römermann, Sonja Bröer, Sebastian Meller, Ingo Gerhauser, Vladan Rankovic, Dandan Li, Claudia Brandt, Marion Bankstahl, Kathrin Töllner, Wolfgang Löscher
Epilepsy may arise following acute brain insults, but no treatments exist that prevent epilepsy in patients at risk. Here we examined whether a combination of two glutamate receptor antagonists, NBQX and ifenprodil, acting at different receptor subtypes, exerts antiepileptogenic effects in the intrahippocampal kainate mouse model of epilepsy. These drugs were administered over 5 days following kainate. Spontaneous seizures were recorded by video/EEG at different intervals up to 3 months. Initial trials showed that drug treatment during the latent period led to higher mortality than treatment after onset of epilepsy, and further, that combined therapy with both drugs caused higher mortality at doses that appear safe when used singly...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28926841/beneficial-combination-of-lacosamide-with-retigabine-in-experimental-animals-an-isobolographic-analysis
#11
Jarogniew J Luszczki, Mirosław Zagaja, Barbara Miziak, Maria W Kondrat-Wrobel, Katarzyna Zaluska, Paula Wroblewska-Luczka, Piotr Adamczuk, Stanislaw J Czuczwar, Magdalena Florek-Luszczki
BACKGROUND/AIM: To isobolographically determine the types of interactions that occur between retigabine and lacosamide (LCM; two third-generation antiepileptic drugs) with respect to their anticonvulsant activity and acute adverse effects (sedation) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male Swiss mice. METHODS: Type I isobolographic analysis for nonparallel dose-response effects for the combination of retigabine with LCM (at the fixed-ratio of 1:1) in both the MES and chimney test in mice was performed...
September 20, 2017: Pharmacology
https://www.readbyqxmd.com/read/28918300/dynamical-properties-of-lfps-from-mice-with-unilateral-injection-of-tent
#12
Eleonora Vannini, Matteo Caleo, Santi Chillemi, Angelo Di Garbo
Local field potential (LFP) recordings were performed from the visual cortex (V1) of a focal epilepsy mouse model. Epilepsy was induced by a unilateral injection of the synaptic blocker tetanus neurotoxin (TeNT). LFP signals were simultaneously recorded from V1 of both hemispheres of each animal under acute and chronic conditions (i.e. during and after the period of TeNT action). All data were analysed by using nonlinear time series methods. Suitable values of the lag time and embedding dimension for phase space reconstruction were estimated by employing well-known methods...
September 13, 2017: Bio Systems
https://www.readbyqxmd.com/read/28913566/adar-rna-editing-in-human-disease-more-to-it-than-meets-the-i
#13
REVIEW
Angela Gallo, Dragana Vukic, David Michalík, Mary A O'Connell, Liam P Keegan
We review the structures and functions of ADARs and their involvements in human diseases. ADAR1 is widely expressed, particularly in the myeloid component of the blood system, and plays a prominent role in promiscuous editing of long dsRNA. Missense mutations that change ADAR1 residues and reduce RNA editing activity cause Aicardi-Goutières Syndrome, a childhood encephalitis and interferonopathy that mimics viral infection and resembles an extreme form of Systemic Lupus Erythmatosus (SLE). In Adar1 mouse mutant models aberrant interferon expression is prevented by eliminating interferon activation signaling from cytoplasmic dsRNA sensors, indicating that unedited cytoplasmic dsRNA drives the immune induction...
September 14, 2017: Human Genetics
https://www.readbyqxmd.com/read/28901011/persistent-aberrant-cortical-phase-amplitude-coupling-following-seizure-treatment-in-absence-epilepsy-models
#14
Atul Maheshwari, Abraham Akbar, Mai Wang, Rachel Marks, Katherine Yu, Suhyeorn Park, Brett L Foster, Jeffrey L Noebels
In childhood absence epilepsy, cortical seizures are brief and intermittent; however there are extended periods without behavioural or electrographic ictal events. This genetic disorder is associated with variable degrees of cognitive dysfunction, but no consistent functional biomarkers that might provide insight into interictal cortical function have been described. Previous work in monogenic mouse models of absence epilepsy have shown that the interictal EEG displays augmented beta/gamma power in homozygous stargazer (stg/stg) mice bearing a presynaptic AMPA receptor defect, but not homozygous tottering (tg/tg) mice with a P/Q type calcium channel mutation...
September 12, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28894505/increased-mitochondrial-mass-and-cytosolic-redox-imbalance-in-hippocampal-astrocytes-of-a-mouse-model-of-rett-syndrome-subcellular-changes-revealed-by-ratiometric-imaging-of-jc-1-and-rogfp1-fluorescence
#15
Dörthe F Bebensee, Karolina Can, Michael Müller
Rett syndrome (RTT) is a neurodevelopmental disorder with mutations in the MECP2 gene. Mostly girls are affected, and an apparently normal development is followed by cognitive impairment, motor dysfunction, epilepsy, and irregular breathing. Various indications suggest mitochondrial dysfunction. In Rett mice, brain ATP levels are reduced, mitochondria are leaking protons, and respiratory complexes are dysregulated. Furthermore, we found in MeCP2-deficient mouse (Mecp2(-/y) ) hippocampus an intensified mitochondrial metabolism and ROS generation...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28867282/trif-contributes-to-epileptogenesis-in-temporal-lobe-epilepsy-during-tlr4-activation
#16
Fa-Xiang Wang, Xiao-Lin Yang, Yuan-Shi Ma, Yu-Jia Wei, Mei-Hua Yang, Xin Chen, Bing Chen, Qian He, Qing-Wu Yang, Hui Yang, Shi-Yong Liu
Increasing evidence indicates that inflammatory processes play a crucial role in the etiopathology of epilepsy and seizure disorders. The Toll/IL-1R domain-containing adapter-inducing IFN-β (TRIF) activated several transcriptions leading to the production of pro-inflammatory cytokines in the central nervous system, which suggests a potential role for TRIF in the epileptogenesis of epilepsy. In this study, we investigated the roles of TRIF in human and mice epileptogenic tissues. Western blot and immunohistochemistry assays showed that the expression of TRIF was significantly upregulated in neurons and glial cells in both human epileptic tissues and mouse models, and positively correlated with seizure frequency...
September 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28844345/the-effect-of-atomoxetine-a-selective-norepinephrine-reuptake-inhibitor-on-respiratory-arrest-and-cardiorespiratory-function-in-the-dba-1-mouse-model-of-sudep
#17
Haiting Zhao, Joseph F Cotten, Xiaoyan Long, Hua-Jun Feng
Sudden unexpected death in epilepsy (SUDEP) is a significant public health burden. The mechanisms of SUDEP are elusive, although cardiorespiratory dysfunction is a likely contributor. Clinical and animal studies indicate that seizure-induced respiratory arrest (S-IRA) is the primary event leading to death in many SUDEP cases. Our prior studies demonstrated that intraperitoneal (IP) injection of atomoxetine, a norepinephrine reuptake inhibitor (NRI) widely used to treat attention deficit hyperactivity disorder, suppresses S-IRA in DBA/1 mice...
August 22, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28842554/cdyl-suppresses-epileptogenesis-in-mice-through-repression-of-axonal-nav1-6-sodium-channel-expression
#18
Yongqing Liu, Shirong Lai, Weining Ma, Wei Ke, Chan Zhang, Shumeng Liu, Yu Zhang, Fei Pei, Shaoyi Li, Ming Yi, Yousheng Shu, Yongfeng Shang, Jing Liang, Zhuo Huang
Impairment of intrinsic plasticity is involved in a range of neurological disorders such as epilepsy. However, how intrinsic excitability is regulated is still not fully understood. Here we report that the epigenetic factor Chromodomain Y-like (CDYL) protein is a critical regulator of the initiation and maintenance of intrinsic neuroplasticity by regulating voltage-gated ion channels in mouse brains. CDYL binds to a regulatory element in the intron region of SCN8A and mainly recruits H3K27me3 activity for transcriptional repression of the gene...
August 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28833459/persistent-seizure-control-in-epileptic-mice-transplanted-with-gamma-aminobutyric-acid-progenitors
#19
Mariana L Casalia, MacKenzie A Howard, Scott C Baraban
OBJECTIVE: A significant proportion of the more than 50 million people worldwide currently suffering with epilepsy are resistant to antiepileptic drugs (AEDs). As an alternative to AEDs, novel therapies based on cell transplantation offer an opportunity for long-lasting modification of epileptic circuits. To develop such a treatment requires careful preclinical studies in a chronic epilepsy model featuring unprovoked seizures, hippocampal histopathology, and behavioral comorbidities. METHODS: Transplantation of progenitor cells from embryonic medial or caudal ganglionic eminence (MGE, CGE) were made in a well-characterized mouse model of status epilepticus-induced epilepsy (systemic pilocarpine)...
August 18, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28831605/neural-stem-cells-and-epilepsy-functional-roles-and-disease-in-a-dish-models
#20
REVIEW
Drew M Thodeson, Rebecca Brulet, Jenny Hsieh
Epilepsy is a disorder of the central nervous system characterized by spontaneous recurrent seizures. Although current therapies exist to control the number and severity of clinical seizures, there are no pharmacological cures or disease-modifying treatments available. Use of transgenic mouse models has allowed an understanding of neural stem cells in their relation to epileptogenesis in mesial temporal lobe epilepsy. Further, with the significant discovery of factors necessary to reprogram adult somatic cell types into pluripotent stem cells, it has become possible to study monogenic epilepsy-in-a-dish using patient-derived neurons...
August 22, 2017: Cell and Tissue Research
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