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epilepsy mouse model

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https://www.readbyqxmd.com/read/28624414/corneal-kindled-c57bl-6-mice-exhibit-saturated-dentate-gyrus-long-term-potentiation-and-associated-memory-deficits-in-the-absence-of-overt-neuron-loss
#1
Gregory J Remigio, Jaycie L Loewen, Sage Heuston, Colin Helgeson, H Steve White, Karen S Wilcox, Peter J West
Memory deficits have a significant impact on the quality of life of patients with epilepsy and currently no effective treatments exist to mitigate this comorbidity. While these cognitive comorbidities can be associated with varying degrees of hippocampal cell death and hippocampal sclerosis, more subtle changes in hippocampal physiology independent of cell loss may underlie memory dysfunction in many epilepsy patients. Accordingly, animal models of epilepsy or epileptic processes exhibiting memory deficits in the absence of cell loss could facilitate novel therapy discovery...
June 15, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28620084/multidimensional-genetic-analysis-of-repeated-seizures-in-the-hybrid-mouse-diversity-panel-reveals-a-novel-epileptogenesis-susceptibility-locus
#2
Russell J Ferland, Jason Smith, Dominick Papandrea, Jessica Gracias, Leah Hains, Sridhar B Kadiyala, Brittany O'Brien, Eun Yong Kang, Barbara S Beyer, Bruce J Herron
Epilepsy has many causes and comorbidities affecting as many as 4% of people in their lifetime. Both idiopathic and symptomatic epilepsies are highly heritable, but genetic factors are difficult to characterize among humans due to complex disease etiologies. Rodent genetic studies have been critical to the discovery of seizure susceptibility loci, including Kcnj10 mutations identified in both mouse and human cohorts. However, genetic analyses of epilepsy phenotypes in mice to date have been carried out as acute studies in seizure-naive animals or in Mendelian models of epilepsy, while humans with epilepsy have a history of recurrent seizures that also modify brain physiology...
June 15, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28605634/atomoxetine-a-norepinephrine-reuptake-inhibitor-reduces-seizure-induced-respiratory-arrest
#3
Honghai Zhang, Haiting Zhao, Hua-Jun Feng
Sudden unexpected death in epilepsy (SUDEP) is a devastating epilepsy complication, and no effective preventive strategies are currently available for this fatal disorder. Clinical and animal studies of SUDEP demonstrate that seizure-induced respiratory arrest (S-IRA) is the primary event leading to death after generalized seizures in many cases. Enhancing brain levels of serotonin reduces S-IRA in animal models relevant to SUDEP, including the DBA/1 mouse. Given that serotonin in the brain plays an important role in modulating respiration and arousal, these findings suggest that deficits in respiration and/or arousal may contribute to S-IRA...
June 9, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28603559/three-immune-mediated-disease-models-induced-by-theiler-s-virus-multiple-sclerosis-seizures-and-myocarditis
#4
Ikuo Tsunoda, Fumitaka Sato, Seiichi Omura, Mitsugu Fujita, Namie Sakiyama, Ah-Mee Park
Theiler's murine encephalomyelitis virus (TMEV) infection has been used as a viral model for multiple sclerosis (MS), as TMEV can induce chronic inflammatory demyelinating lesions with viral persistence in the spinal cord of SJL/J mice. In contrast, when C57BL/6 mice are infected with TMEV, the mice can clear the virus from the central nervous system (CNS), without viral persistence or demyelination, but develop seizures and hippocampal sclerosis, which has been used as a viral model for seizures/epilepsy. In the two TMEV-induced CNS disease models, not only viral infection, but also immune responses contribute to the pathogenesis...
November 2016: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/28602636/extensive-phenotyping-of-two-arx-polyalanine-expansion-mutation-mouse-models-that-span-clinical-spectrum-of-intellectual-disability-and-epilepsy
#5
Matilda R Jackson, Kristie Lee, Tessa Mattiske, Emily J Jaehne, Ezgi Ozturk, Bernhard T Baune, Terence J O'Brien, Nigel Jones, Cheryl Shoubridge
The Aristaless-related homeobox gene (ARX) is a known intellectual disability (ID) gene that frequently presents with X-linked infantile spasm syndrome as a comorbidity. ID with epilepsy in children is a chronic and devastating disorder that has poor treatment options and disease outcomes. To gain a better understanding of the role that mutations in ARX play in ID and epilepsy, we investigate ARX patient mutations modelled in mice. Over half of all ARX mutations result from expansions of the first two polyalanine (PA1 and PA2 respectively) tracts...
June 8, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28589518/forty-years-of-sodium-channels-structure-function-pharmacology-and-epilepsy
#6
William A Catterall
Voltage-gated sodium channels initiate action potentials in brain neurons. In the 1970s, much was known about the function of sodium channels from measurements of ionic currents using the voltage clamp method, but there was no information about the sodium channel molecules themselves. As a postdoctoral fellow and staff scientist at the National Institutes of Health, I developed neurotoxins as molecular probes of sodium channels in cultured neuroblastoma cells. During those years, Bruce Ransom and I crossed paths as members of the laboratories of Marshall Nirenberg and Philip Nelson and shared insights about sodium channels in neuroblastoma cells from my work and electrical excitability and synaptic transmission in cultured spinal cord neurons from Bruce's pioneering electrophysiological studies...
June 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28584127/dynamic-changes-in-murine-forebrain-mir-211-expression-associate-with-cholinergic-imbalances-and-epileptiform-activity
#7
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/28556246/cacna1g-is-a-genetic-modifier-of-epilepsy-in-a-mouse-model-of-dravet-syndrome
#8
Jeffrey D Calhoun, Nicole A Hawkins, Nicole J Zachwieja, Jennifer A Kearney
Dravet syndrome, an early onset epileptic encephalopathy, is most often caused by de novo mutation of the neuronal voltage-gated sodium channel gene SCN1A. Mouse models with deletion of Scn1a recapitulate Dravet syndrome phenotypes, including spontaneous generalized tonic-clonic seizures, susceptibility to seizures induced by elevated body temperature, and elevated risk of sudden unexpected death in epilepsy. Importantly, the epilepsy phenotype of Dravet mouse models is highly strain-dependent, suggesting a strong influence of genetic modifiers...
May 28, 2017: Epilepsia
https://www.readbyqxmd.com/read/28542864/circadian-clustering-of-spontaneous-epileptic-seizures-emerges-after-pilocarpine-induced-status-epilepticus
#9
Julika Pitsch, Albert J Becker, Susanne Schoch, Johannes Alexander Müller, Marco de Curtis, Vadym Gnatkovsky
OBJECTIVE: Seizures in mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis are thought to develop with various latency intervals after an initial transient brain insult. To study seizure dynamics after an initial transient precipitating insult in a systematic fashion, we utilized continuous video-electroencephalography (EEG) monitoring after the induction of status epilepticus (SE) in a mouse MTLE model. METHODS: Continuous 24/7 video/telemetric hippocampal EEG recordings in the systemic pilocarpine MTLE mouse model...
May 24, 2017: Epilepsia
https://www.readbyqxmd.com/read/28536304/abnormal-glycogen-chain-length-pattern-not-hyperphosphorylation-is-critical-in-lafora-disease
#10
Felix Nitschke, Mitchell A Sullivan, Peixiang Wang, Xiaochu Zhao, Erin E Chown, Ami M Perri, Lori Israelian, Lucia Juana-López, Paola Bovolenta, Santiago Rodríguez de Córdoba, Martin Steup, Berge A Minassian
Lafora disease (LD) is a fatal progressive epilepsy essentially caused by loss-of-function mutations in the glycogen phosphatase laforin or the ubiquitin E3 ligase malin. Glycogen in LD is hyperphosphorylated and poorly hydrosoluble. It precipitates and accumulates into neurotoxic Lafora bodies (LBs). The leading LD hypothesis that hyperphosphorylation causes the insolubility was recently challenged by the observation that phosphatase-inactive laforin rescues the laforin-deficient LD mouse model, apparently through correction of a general autophagy impairment...
May 23, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28526576/carvacrol-promotes-neuroprotection-in-the-mouse-hemiparkinsonian-model
#11
L M Dati, H Ulrich, C C Real, Z P Feng, H S Sun, L R Britto
Carvacrol is a monoterpene that has been linked to neuroprotection in several animal models of neurodegeneration, including ischemia, epilepsy and traumatic neuronal injury. In this study, we investigated the effects of carvacrol (i.p.) upon the neurodegeneration induced by 6-hydroxy-dopamine unilateral intrastriatal injections in mice. We have also used the cylinder test to assess the behavioral effects of carvacrol in that model of Parkinson's disease, and immunoblots to evaluate the levels of caspase-3 and TRPM7, one of major targets of carvacrol...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28521116/efficacy-of-anticonvulsant-substances-in-the-6hz-seizure-test-comparison-of-two-rodent-species
#12
Elise Esneault, Guillaume Peyon, Vincent Castagné
Usually performed in the mouse, the 6Hz seizure test is used for screening potential new anticonvulsant substances against complex partial seizures. Nevertheless, advanced models of temporal lobe epilepsy (TLE) are more often performed in rats, so that possible species-related differences may complicate the development of anticonvulsant substances. The aim of the present study was to evaluate the feasibility of adapting the 6Hz test in the rat. We first compared the effects of increasing current intensities for inducing seizures in the mouse and in the rat...
May 10, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28521115/anticonvulsant-profile-of-the-neuroactive-steroid-sge-516-in-animal-models
#13
Rebecca S Hammond, Alison L Althaus, Michael A Ackley, Carla Maciag, Gabriel Martinez Botella, Francesco G Salituro, Albert J Robichaud, James J Doherty
Despite the availability of multiple antiepileptic drugs (AED), failure to adequately control seizures is a challenge for approximately one third of epilepsy patients, and new therapies with a differentiated mechanism of action are needed. The neuroactive steroid, SGE-516, is a positive allosteric modulator of both gamma- and delta-containing GABAA receptors. This broad GABAA receptor activity differentiates neuroactive steroids like SGE-516 from benzodiazepines, a class of anticonvulsants which have been shown in vitro to selectively target gamma-subunit containing GABAA receptors...
May 7, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28520841/chronic-inflammatory-pain-impairs-mglur5-mediated-depolarization-induced-suppression-of-excitation-in-the-anterior-cingulate-cortex
#14
Baolin Guo, Jiaqi Wang, Han Yao, Keke Ren, Jing Chen, Jing Yang, Guohong Cai, Haiying Liu, Yunlong Fan, Wenting Wang, Shengxi Wu
The anterior cingulate cortex (ACC) is a critical hub for nociceptive perception and pain-related anxiety. Long-term synaptic plasticity in ACC was found to be important for chronic inflammatory pain and pain-related anxiety. As short-term synaptic plasticity, depolarization-induced suppression of excitation (DSE) is involved in several conditions, such as chronic stress, epilepsy, and autism. However, it is still unknown whether DSE in the ACC is involved in the central sensitization of pain and anxiety. Using a whole-cell patch clamp, calcium imaging, western blot, and behavioral testing, we found that DSE was induced by a 2 s depolarization in postsynaptic pyramidal cells in ACC...
May 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28506618/the-ptz-kindling-mouse-model-of-epilepsy-exhibits-exploratory-drive-deficits-and-aberrant-activity-amongst-vta-dopamine-neurons-in-both-familiar-and-novel-space
#15
Mahboubeh Ahmadi, Jean-Philippe Dufour, Erich Seifritz, Javad Mirnajafi-Zadeh, Bechara J Saab
Recurrent seizures that define epilepsy are often accompanied by psychosocial problems and cognitive deficits with incompletely understood aetiology. We therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to examine potential seizure-associated neuropathologies, focusing on motivation, memory and novel-environment-induced activation of midbrain dopaminergic neurons. In addition to recurrent seizures, we found that PTZ kindling led to a strong suppression of novelty-driven exploration while largely sparing fear-driven exploration...
May 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28505490/heat-induced-temperature-dysregulation-and-seizures-in-dravet-syndrome-gefs-gabrg2-q390x-mice
#16
Timothy A Warner, Zhong Liu, Robert L Macdonald, Jing-Qiong Kang
It has been established that febrile seizures and its extended syndromes like generalized epilepsy with febrile seizures (FS) plus (GEFS+) and Dravet syndrome have been associated with mutations especially in SCN1A and GABRG2 genes. In patients, the onset of FS is likely due to the combined effect of temperature and inflammation in genetically vulnerable individuals because fever is often associated with infection. Much effort has been spent to understand the mechanisms underlying fever induction of seizures...
August 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28502704/ketogenic-diet-leads-to-o-glcnac-modification-in-the-btbr-t-tf-j-mouse-model-of-autism
#17
Christopher Newell, Virginia L Johnsen, Nellie C Yee, Warren J Xu, Matthias S Klein, Aneal Khan, Jong M Rho, Jane Shearer
BACKGROUND: Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBR(T+tf/j) (BTBR) mouse model of ASD...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28497109/hippocampal-tnf%C3%AE-signaling-contributes-to-seizure-generation-in-an-infection-induced-mouse-model-of-limbic-epilepsy
#18
Dipan C Patel, Glenna Wallis, E Jill Dahle, Pallavi B McElroy, Kyle E Thomson, Raymond J Tesi, David E Szymkowski, Peter J West, Roy M Smeal, Manisha Patel, Robert S Fujinami, H Steve White, Karen S Wilcox
Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler's murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28492982/adenosine-a1-receptors-play-an-important-protective-role-against-cognitive-impairment-and-long-term-potentiation-inhibition-in-a-pentylenetetrazol-mouse-model-of-epilepsy
#19
Qing Zhou, Suiqiang Zhu, Yuchen Guo, Lifei Lian, Qi Hu, Xiaoyan Liu, Feng Xu, Na Zhang, Huicong Kang
Epilepsy is a complicated neurological disorder that occurs worldwide and features several kinds of comorbidities in addition to recurrent seizures. One of the most common comorbidities is cognitive impairment, which seriously affects patients' quality of life. Through activating pre- and postsynaptic adenosine A1 receptors (A1Rs), adenosine has demonstrated anticonvulsant and neuroprotective effects in many epileptic animal models. However, whether the neuroprotective effect of A1Rs will protect cognition during epileptogenesis remains unknown...
May 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28491900/screening-of-conventional-anticonvulsants-in-a-genetic-mouse-model-of-epilepsy
#20
Nicole A Hawkins, Lyndsey L Anderson, Tracy S Gertler, Linda Laux, Alfred L George, Jennifer A Kearney
OBJECTIVE: Epilepsy is a common neurological disorder that affects 1% of the population. Approximately, 30% of individuals with epilepsy are refractory to treatment, highlighting the need for novel therapies. Conventional anticonvulsant screening relies predominantly on induced seizure models. However, these models may not be etiologically relevant for genetic epilepsies. Mutations in SCN1A are a common cause of Dravet Syndrome, a severe epileptic encephalopathy. Dravet syndrome typically begins in infancy with seizures provoked by fever and then progresses to include afebrile pleomorphic seizure types...
May 2017: Annals of Clinical and Translational Neurology
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