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https://www.readbyqxmd.com/read/30545302/when-pitch-adds-to-volume-coregulation-of-transcript-diversity-predicts-gene-function
#1
Alejandro Cáceres, Juan R González
BACKGROUND: Genes corregulate their overall transcript volumes to perform their physiological functions. However, it is unknown if they additionally coregulate their transcript diversities. We studied the reliability, consistency and functional associations of co-splicing correlations of genes of interest, across two independent studies, multiple tissues and two statistical methods. We thoroughly investigated the reproducibility of co-splicing correlations of APP, the candidate gene of Azheimer's disease (AD)...
December 13, 2018: BMC Genomics
https://www.readbyqxmd.com/read/30451289/chronic-overexpression-of-ubiquitin-impairs-learning-reduces-synaptic-plasticity-and-enhances-gria-receptor-turnover-in-mice
#2
Jada H Vaden, Tina Tian, Samantha Golf, John W McLean, Julie A Wilson, Scott M Wilson
Ubiquitin is an essential signaling protein that controls many different cellular processes. While cellular ubiquitin levels normally cycle between pools of free and conjugated ubiquitin, the balance of these ubiquitin pools can be shifted by exposure to a variety of cellular stresses. Altered ubiquitin pools are also observed in several neurological disorders, suggesting that imbalances in ubiquitin homeostasis may contribute to neuronal dysfunction. To examine the effects of increased ubiquitin levels on the mammalian nervous system, we generated transgenic mice that express ubiquitin under the control of the Thy1...
November 19, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/30446525/quantitative-assessment-of-the-association-between-gria1-polymorphisms-and-migraine-risk
#3
Xueren Gao, Jianguo Wang
PURPOSE: The association between GRIA1  rs548294 G>A and rs2195450 C>T polymorphisms and migraine risk has been reported in several case-control studies. However, the results of studies are inconsistent. Thus, we conducted a meta-analysis to more precisely estimate the association of the two polymorphisms with migraine risk.  Methods: Eligible studies were retrieved and screened from the online databases (EMBASE, PubMed, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure)...
November 16, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/30347267/prrt2-deficiency-induces-paroxysmal-kinesigenic-dyskinesia-by-influencing-synaptic-function-in-the-primary-motor-cortex-of-rats
#4
Juan Mo, Bantong Wang, Xilin Zhu, Xiaopan Wu, Ying Liu
Proline-rich transmembrane protein 2 (PRRT2) was identified as the causative gene of paroxysmal kinesigenic choreoathetosis (PKC) as well as various other neurological diseases. However, the molecular mechanisms of how mutant PRRT2 leads to abnormal synaptic function and triggers PKC are still obscure. We generated a Prrt2 truncated mutant rat model which shows spontaneous PKC-like attacks with a relative low frequency as well as increased susceptibility to pentylenetetrazol (PTZ)-induced seizures. We demonstrate that PRRT2 is expressed on both pre- and post-synaptic membranes in the M1 cortex...
October 19, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/30310176/aberrant-receptor-tyrosine-kinase-signaling-in-lipofibromatosis-a-clinicopathological-and-molecular-genetic-study-of-20-cases
#5
Alyaa Al-Ibraheemi, Andrew L Folpe, Antonio R Perez-Atayde, Kyle Perry, Jakob Hofvander, Elsa Arbajian, Linda Magnusson, Jenny Nilsson, Fredrik Mertens
Lipofibromatosis is a rare pediatric soft tissue tumor with predilection for the hands and feet. Previously considered to represent "infantile fibromatosis", lipofibromatosis has distinctive morphological features, with mature adipose tissue, short fascicles of bland fibroblastic cells, and lipoblast-like cells. Very little is known about the genetic underpinnings of lipofibromatosis. Prompted by our finding of the FN1-EGF gene fusion, previously shown to be a characteristic feature of calcifying aponeurotic fibroma (CAF), in a morphologically typical case of lipofibromatosis that recurred showing features of CAF, we studied a cohort of 20 cases of lipofibromatosis for this and other genetic events...
October 11, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/30287307/does-acute-heat-stress-differentially-modulate-expression-of-ionotropic-neurotransmitter-receptors-in-the-rvlm-of-young-and-aged-f344-rats
#6
Hitesh N Pawar, Sivasai Balivada, Michael J Kenney
The rostral ventral lateral medulla (RVLM) is a brainstem area that plays a role in regulating numerous physiological systems, especially their responsiveness to acute stress. Aging affects the responsiveness of RVLM neural circuits to acute stress. Based on the relationship between ionotropic neurotransmitter receptors in the RVLM and the physiological functions mediated via activation of these receptors, we hypothesized that in response to acute heat stress the expression of ionotropic neurotransmitter receptors in the RVLM of aged rats would be characterized by upregulation of inhibitory subunits and downregulation of excitatory subunits...
November 20, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/30144237/increased-cocaine-self-administration-in-rats-lacking-the-serotonin-transporter-a-role-for-glutamatergic-signaling-in-the-habenula
#7
Lucia Caffino, Michel M M Verheij, Lin Que, Chao Guo, Judith R Homberg, Fabio Fumagalli
Serotonin (5-HT) and the habenula (Hb) contribute to motivational and emotional states such as depression and drug abuse. The dorsal raphe nucleus, where 5-HT neurons originate, and the Hb are anatomically and reciprocally interconnected. Evidence exists that 5-HT influences Hb glutamatergic transmission. Using serotonin transporter knockout (SERT-/- ) rats, which show depression-like behavior and increased cocaine intake, we investigated the effect of SERT reduction on expression of genes involved in glutamate neurotransmission under both baseline conditions as well as after short-access or long-access cocaine (ShA and LgA, respectively) intake...
August 24, 2018: Addiction Biology
https://www.readbyqxmd.com/read/30108203/absent-sleep-eeg-spindle-activity-in-glua1-gria1-knockout-mice-relevance-to-neuropsychiatric-disorders
#8
Gauri Ang, Laura E McKillop, Ross Purple, Cristina Blanco-Duque, Stuart N Peirson, Russell G Foster, Paul J Harrison, Rolf Sprengel, Kay E Davies, Peter L Oliver, David M Bannerman, Vladyslav V Vyazovskiy
Sleep EEG spindles have been implicated in attention, sensory processing, synaptic plasticity and memory consolidation. In humans, deficits in sleep spindles have been reported in a wide range of neurological and psychiatric disorders, including schizophrenia. Genome-wide association studies have suggested a link between schizophrenia and genes associated with synaptic plasticity, including the Gria1 gene which codes for the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor...
August 14, 2018: Translational Psychiatry
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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