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https://www.readbyqxmd.com/read/30053506/selective-deletion-of-glutamine-synthetase-in-the-mouse-cerebral-cortex-induces-glial-dysfunction-and-vascular-impairment-that-precede-epilepsy-and-neurodegeneration
#1
Yun Zhou, Roni Dhaher, Maxime Parent, Qiu-Xiang Hu, Bjørnar Hassel, Siu-Pok Yee, Fahmeed Hyder, Shaun E Gruenbaum, Tore Eid, Niels Christian Danbolt
Glutamate-ammonia ligase (glutamine synthetase; Glul) is enriched in astrocytes and serves as the primary enzyme for ammonia detoxification and glutamate inactivation in the brain. Loss of astroglial Glul is reported in hippocampi of epileptic patients, but the mechanism by which Glul deficiency might cause disease remains elusive. Here we created a novel mouse model by selectively deleting Glul in the hippocampus and neocortex. The Glul deficient mice were born without any apparent malformations and behaved unremarkably until postnatal week three...
July 24, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29985178/clozapine-pharmacogenomics-a-review-of-efficacy-pharmacokinetics-and-agranulocytosis
#2
Kevin J Li, Haley V Solomon, Lynn E DeLisi
PURPOSE OF REVIEW: To examine recent literature regarding the pharmacogenomics of clozapine (CLZ) efficacy, pharmacokinetics, and agranulocytosis. RECENT FINDINGS: Several genetic loci (FKBP5, NR3C1, BDNF, NTRK2) along the hypothalamic pituitary adrenal axis have been investigated as targets for CLZ response. Homozygous FKBP5-rs1360780, homozygous NTRK2-rs1778929, and homozygous NTRK2-rs10465180 conferred significant risks for CLZ nonresponse - 2.11x risk [95% confidence interval (CI) 1...
September 2018: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/29976232/immature-like-molecular-expression-patterns-in-the-hippocampus-of-a-mouse-model-of-dementia-with-lewy-body-linked-mutant-%C3%AE-synuclein
#3
Hideo Hagihara, Masayo Fujita, Juzoh Umemori, Makoto Hashimoto, Tsuyoshi Miyakawa
AIM: Maturation abnormalities of the brain cells have been suggested in several neuropsychiatric disorders, including schizophrenia, bipolar disorder, autism spectrum disorders, and epilepsy. In this study, we examined the expression patterns of neuronal maturation markers in the brain of a mouse model of dementia with Lewy body-linked mutant β-synuclein (βS), especially in the hippocampus, to explore whether such brain abnormalities occur in neurodegenerative disorders as well. METHODS: Quantitative PCR (qPCR) and immunohistochemical analyses were performed using the hippocampus of 14-month-old P123H βS transgenic (Tg) mice to evaluate the expression of molecular markers for maturation of dentate granule cells...
July 6, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29914235/serum-s100b-nse-and-gria1-levels-as-neurological-biomarkers-in-lead-exposure
#4
Esra Fırat Oğuz, Fatma Meriç Yılmaz, Engin Tutkun, Ömer Hınç Yılmaz, Müjgan Ercan, Sevilay Sezer
Background/aim: The central nervous system is one of the major targets in lead exposure. Biomarkers for the diagnosis and follow-up of lead exposure have not been identified. In this study, serum S100B, neuron-specific enolase (NSE), and glutamate receptor 1 (GRIA1) levels were determined as possible biomarkers for lead neurotoxicity. Material and methods: Twenty-five subjects with chronic lead exposure and 25 controls were included in the study. NSE and S100B were measured by electrochemiluminescence immunoassay with a Cobas E601 analyzer...
June 14, 2018: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/29695692/-multiplex-genotyping-of-allelic-variants-of-genes-involved-in-metabolizing-antileukemic-drugs
#5
D O Fesenko, M A Avdonina, L G Gukasyan, S A Surzhikov, A V Chudinov, A S Zasedatelev, T V Nasedkina
A biochip, primer set, and genotyping protocol were developed to simultaneously address 16 single nucleotide polymorphisms in antileukemic drug metabolism genes, including TPMT, ITPA, MTHFR, SLCO1B1, SLC19A1, NR3C1, GRIA1, ASNS, MTRR, and ABCB1. The genotyping procedure included a one-round multiplex polymerase chain reaction (PCR) with simultaneous incorporation of a fluorescent label into the PCR product and subsequent hybridization on a biochip with immobilized probes. The method was used to test 65 DNA samples of leukemia patients...
March 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29651133/refined-protocols-of-tamoxifen-injection-for-inducible-dna-recombination-in-mouse-astroglia
#6
Hannah M Jahn, Carmen V Kasakow, Andreas Helfer, Julian Michely, Alexei Verkhratsky, Hans H Maurer, Anja Scheller, Frank Kirchhoff
Inducible DNA recombination of floxed alleles in vivo by liver metabolites of tamoxifen (TAM) is an important tool to study gene functions. Here, we describe protocols for optimal DNA recombination in astrocytes, based on the GLAST-CreERT2 /loxP system. In addition, we demonstrate that quantification of genomic recombination allows to determine the proportion of cell types in various brain regions. We analyzed the presence and clearance of TAM and its metabolites (N-desmethyl-tamoxifen, 4-hydroxytamoxifen and endoxifen) in brain and serum of mice by liquid chromatographic-high resolution-tandem mass spectrometry (LC-HR-MS/MS) and assessed optimal injection protocols by quantitative RT-PCR of several floxed target genes (p2ry1, gria1, gabbr1 and Rosa26-tdTomato locus)...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29391390/ulk4-regulates-gabaergic-signaling-and-anxiety-related-behavior
#7
Min Liu, Marie Fitzgibbon, Yanqin Wang, Jamie Reilly, Xiaohong Qian, Timothy O'Brien, Steve Clapcote, Sanbing Shen, Michelle Roche
Excitation/inhibition imbalance has been proposed as a fundamental mechanism in the pathogenesis of neuropsychiatric and neurodevelopmental disorders, in which copy number variations of the Unc-51 like kinase 4 (ULK4) gene encoding a putative Serine/Threonine kinase have been reported in approximately 1/1000 of patients suffering pleiotropic clinical conditions of schizophrenia, depression, autistic spectrum disorder (ASD), developmental delay, language delay, intellectual disability, or behavioral disorder...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29338492/genetic-variation-of-gria3-gene-is-associated-with-vulnerability-to-methamphetamine-dependence-and-its-associated-psychosis
#8
Sri-Arun Iamjan, Samur Thanoi, Paritat Watiktinkorn, Gavin P Reynolds, Sutisa Nudmamud-Thanoi
Methamphetamine (METH) is an addictive psychostimulant drug commonly leading to schizophrenia-like psychotic symptoms. Disturbances in glutamatergic neurotransmission have been proposed as neurobiological mechanisms and the α-amino-3 hydroxy-5 methyl-4 isoxazole propionic acid (AMPA) glutamate receptor has been implicated in these processes. Moreover, genetic variants in GRIAs, genes encoding AMPA receptor subunits, have been observed in association with both drug dependence and psychosis. We hypothesized that variation of GRIA genes may be associated with METH dependence and METH-induced psychosis...
March 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29247759/repeated-methamphetamine-and-modafinil-induce-differential-cognitive-effects-and-specific-histone-acetylation-and-dna-methylation-profiles-in-the-mouse-medial-prefrontal-cortex
#9
Betina González, Subramaniam Jayanthi, Natalia Gomez, Oscar V Torres, Máximo H Sosa, Alejandra Bernardi, Francisco J Urbano, Edgar García-Rill, Jean-Lud Cadet, Verónica Bisagno
Methamphetamine (METH) and modafinil are psychostimulants with different long-term cognitive profiles: METH is addictive and leads to cognitive decline, whereas modafinil has little abuse liability and is a cognitive enhancer. Increasing evidence implicates epigenetic mechanisms of gene regulation behind the lasting changes that drugs of abuse and other psychotropic compounds induce in the brain, like the control of gene expression by histones 3 and 4 tails acetylation (H3ac and H4ac) and DNA cytosine methylation (5-mC)...
March 2, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29230395/thc-treatment-alters-glutamate-receptor-gene-expression-in-human-stem-cell-derived-neurons
#10
Ifeanyi V Obiorah, Hamza Muhammad, Khalifa Stafford, Erin K Flaherty, Kristen J Brennand
Given the cognitive and behavioral effects following in utero Δ9-tetrahydrocannabinol (THC) exposure that have been reported in humans and rodents, it is critical to understand the precise consequences of THC on developing human neurons. Here, we utilize excitatory neurons derived from human-induced pluripotent stem cells (hiPSCs), and report that in vitro THC exposure reduced expression of glutamate receptor subunit genes ( GRIA1 , GRIA2, GRIN2A , and GRIN2B ). By expanding these studies across hiPSC-derived neurons from individuals with a variety of genotypes, we believe that a hiPSC-based model will facilitate studies of the interaction of THC exposure and the genetic risk factors underlying neuropsychiatric disease vulnerability...
November 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28979808/analysis-of-bladder-cancer-tumor-cpg-methylation-and-gene-expression-within-the-cancer-genome-atlas-identifies-gria1-as-a-prognostic-biomarker-for-basal-like-bladder-cancer
#11
Sloane K Tilley, William Y Kim, Rebecca C Fry
Increased methylation levels at cytosines proximal to guanines (CpG) in the promoter regions of tumor suppressor genes have been reported to play an important role in the development and progression of bladder cancer. In this study, we conducted a genome-wide analysis using data from The Cancer Genome Atlas to better characterize CpG methylation and mRNA expression patterns in urothelial carcinomas and to identify new epigenetic biomarkers of survival. Across 408 tumors, we identified 223 genes that displayed significant relationships between CpG methylation and mRNA expression levels...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28785046/glua1-ampar-subunit-deletion-reduces-the-hedonic-response-to-sucrose-but-leaves-satiety-and-conditioned-responses-intact
#12
Joseph M Austen, Rolf Sprengel, David J Sanderson
The GluA1 subunit of the AMPA receptor has been implicated in schizophrenia. While GluA1 is important for cognition, it is not clear what the role of GluA1 is in hedonic responses that are relevant to the negative symptoms of disorders such as schizophrenia. Here, we tested mice that lack GluA1 (Gria1 (-/-) mice) on consumption of sucrose solutions using a licking microstructure analysis. GluA1 deletion drastically reduced palatability (as measured by the mean lick cluster size) across a range of sucrose concentrations...
August 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28780133/altered-glua1-gria1-function-and-accumbal-synaptic-plasticity-in-the-clock%C3%AE-19-model-of-bipolar-mania
#13
Puja K Parekh, Darius Becker-Krail, Poornima Sundaravelu, Shinsuke Ishigaki, Haruo Okado, Gen Sobue, Yanhua Huang, Colleen A McClung
BACKGROUND: Disruptions in circadian rhythms are associated with an increased risk for bipolar disorder. Moreover, studies show that the circadian protein CLOCK (circadian locomotor output cycles kaput) is involved in regulating monoaminergic systems and mood-related behavior. However, the molecular and synaptic mechanisms underlying this relationship remain poorly understood. METHODS: Using ex vivo whole-cell patch-clamp electrophysiology in ClockΔ19 mutant and wild-type mice we characterized alterations in excitatory synaptic transmission, strength, and intrinsic excitability of nucleus accumbens (NAc) neurons...
June 27, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28628100/hotspots-of-missense-mutation-identify-neurodevelopmental-disorder-genes-and-functional-domains
#14
Madeleine R Geisheker, Gabriel Heymann, Tianyun Wang, Bradley P Coe, Tychele N Turner, Holly A F Stessman, Kendra Hoekzema, Malin Kvarnung, Marie Shaw, Kathryn Friend, Jan Liebelt, Christopher Barnett, Elizabeth M Thompson, Eric Haan, Hui Guo, Britt-Marie Anderlid, Ann Nordgren, Anna Lindstrand, Geert Vandeweyer, Antonino Alberti, Emanuela Avola, Mirella Vinci, Stefania Giusto, Tiziano Pramparo, Karen Pierce, Srinivasa Nalabolu, Jacob J Michaelson, Zdenek Sedlacek, Gijs W E Santen, Hilde Peeters, Hakon Hakonarson, Eric Courchesne, Corrado Romano, R Frank Kooy, Raphael A Bernier, Magnus Nordenskjöld, Jozef Gecz, Kun Xia, Larry S Zweifel, Evan E Eichler
Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,688 patients with NDD identified 21 new patients with identical missense mutations...
August 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28496171/altered-balance-of-excitatory-and-inhibitory-learning-in-a-genetically-modified-mouse-model-of-glutamatergic-dysfunction-relevant-to-schizophrenia
#15
David J Sanderson, Aletheia Lee, Rolf Sprengel, Peter H Seeburg, Paul J Harrison, David M Bannerman
The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in schizophrenia. Gria1 knockout in mice results in recently experienced stimuli acquiring aberrantly high salience. This suggests that GluA1 may be important for learning that is sensitive to the temporal contiguity between events. To test this, mice were trained on a Pavlovian trace conditioning procedure in which the presentation of an auditory cue and food were separated by a temporal interval. Wild-type mice initially learnt, but with prolonged training came to withhold responding during the trace-conditioned cue, responding less than for another cue that was nonreinforced...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28346676/corrigendum-genetic-variations-in-gria1-on-chromosome-5q33-related-to-asparaginase-hypersensitivity
#16
(no author information available yet)
No abstract text is available yet for this article.
November 2014: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28277565/pharmacogenetic-analysis-of-functional-glutamate-system-gene-variants-and-clinical-response-to-clozapine
#17
Danielle L Taylor, Arun K Tiwari, Jeffrey A Lieberman, Steven G Potkin, Herbert Y Meltzer, Joanne Knight, Gary Remington, Daniel J Müller, James L Kennedy
Altered glutamate neurotransmission is implicated in the etiology of schizophrenia (SCZ) and the pharmacogenetics of response to clozapine (CLZ), which is the drug of choice for treatment-resistant SCZ. Response to antipsychotic therapy is highly variable, although twin studies suggest a genetic component. We investigated the association of 10 glutamate system gene variants with CLZ response using standard genotyping procedures. GRM2 (rs4067 and rs2518461), SLC1A2 (rs4354668, rs4534557, and rs2901534), SLC6A9 (rs12037805, rs1978195, and rs16831558), GRIA1 (rs2195450), and GAD1 (rs3749034) were typed in 163 European SCZ/schizoaffective disorder patients deemed resistant or intolerant to previous pharmacotherapy...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28259867/review-of-pharmacogenetics-studies-of-l-asparaginase-hypersensitivity-in-acute-lymphoblastic-leukemia-points-to-variants-in-the-gria1-gene
#18
REVIEW
Maria Lopez-Santillan, Leire Iparraguirre, Idoia Martin-Guerrero, Angela Gutierrez-Camino, Africa Garcia-Orad
Acute lymphoblastic leukemia (ALL) is a major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients who experience severe adverse events. L-Asparaginase is an effective antineoplastic agent used in chemotherapy of ALL. Despite its indisputable indication, hypersensitivity reactions are common. In those cases, discontinuation of treatment is usually needed and anti-asparaginase antibody production may also attenuate asparaginase activity, compromising its antileukemic effect...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28186680/the-group-ii-metabotropic-glutamate-receptor-agonist-ly354740-and-the-d2-receptor-antagonist-haloperidol-reduce-locomotor-hyperactivity-but-fail-to-rescue-spatial-working-memory-in-glua1-knockout-mice
#19
Thomas Boerner, Alexei M Bygrave, Jingkai Chen, Anushka Fernando, Stephanie Jackson, Chris Barkus, Rolf Sprengel, Peter H Seeburg, Paul J Harrison, Gary Gilmour, David M Bannerman, David J Sanderson
Group II metabotropic glutamate receptor agonists have been suggested as potential anti-psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non-competitive N-methyl-d-aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome-wide association studies...
April 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27774052/altered-expression-of-genes-encoding-neurotransmitter-receptors-in-gnrh-neurons-of-proestrous-mice
#20
Csaba Vastagh, Annie Rodolosse, Norbert Solymosi, Zsolt Liposits
Gonadotropin-releasing hormone (GnRH) neurons play a key role in the central regulation of reproduction. In proestrous female mice, estradiol triggers the pre-ovulatory GnRH surge, however, its impact on the expression of neurotransmitter receptor genes in GnRH neurons has not been explored yet. We hypothesized that proestrus is accompanied by substantial changes in the expression profile of genes coding for neurotransmitter receptors in GnRH neurons. We compared the transcriptome of GnRH neurons obtained from intact, proestrous, and metestrous female GnRH-GFP transgenic mice, respectively...
2016: Frontiers in Cellular Neuroscience
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