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https://www.readbyqxmd.com/read/29704590/protective-influences-of-n-acetylcysteine-against-alcohol-abstinence-induced-depression-by-regulating-biochemical-and-grin2a-grin2b-gene-expression-of-nmda-receptor-signaling-pathway-in-rats
#1
Rutuja Yawalkar, Harish Changotra, Girdhari Lal Gupta
Evidences have indicated a high degree of comorbidity of alcoholism and depression. N-acetylcysteine (NAC) has shown its clinical efficiency in the treatment of several psychiatric disorders and is identified as a multi-target acting drug. The ability of NAC to prevent alcohol abstinence-induced depression-like effects and underlying mechanism(s) have not been adequately addressed. This study was aimed to investigate the beneficial effects of NAC in the alcohol abstinence-induced depression developed following long-term voluntary alcohol intake...
April 25, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29616445/voluntary-exercise-during-adolescence-mitigated-negative-the-effects-of-maternal-separation-stress-on-the-depressive-like-behaviors-of-adult-male-rats-role-of-nmda-receptors
#2
Forouzan Fattahi Masrour, Maghsoud Peeri, Mohammad Ali Azarbayjani, Mir-Jamal Hosseini
Evidence indicates that experiencing early-life stress (ELS) is a risk factor for the development of mental disorders such as depression. Maternal separation stress (MS) is a valid animal model of ELS that caused to induce long-lasting effects on the brain and behaviors of animals. It hypothesized that adolescence is a critical stage in which the brain is still developing, and applying (non)pharmacological therapies in this period may attenuate the effects of ELS on the brain and behavior. Male rats were subjected to MS from postnatal day (PND) 2-14, and the stressed animals were then treated with (1) chronic fluoxetine (FLX) (5 mg/kg) and (2) voluntary running wheel exercise (RW) from PND 30, for 30 days...
April 3, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29564678/weighted-burden-analysis-of-exome-sequenced-case-control-sample-implicates-synaptic-genes-in-schizophrenia-aetiology
#3
David Curtis, Leda Coelewij, Shou-Hwa Liu, Jack Humphrey, Richard Mott
A previous study of exome-sequenced schizophrenia cases and controls reported an excess of singleton, gene-disruptive variants among cases, concentrated in particular gene sets. The dataset included a number of subjects with a substantial Finnish contribution to ancestry. We have reanalysed the same dataset after removal of these subjects and we have also included non-singleton variants of all types using a weighted burden test which assigns higher weights to variants predicted to have a greater effect on protein function...
March 21, 2018: Behavior Genetics
https://www.readbyqxmd.com/read/29552280/identification-and-analysis-of-hub-genes-and-networks-related-to-hypoxia-preconditioning-in-mice-no-035215
#4
Haiting Cheng, Can Cui, Shousi Lu, Binbin Xia, Xiaorong Li, Pinxiang Xu, Ming Xue
Hypoxia preconditioning is an effective strategy of intrinsic cell protection. An acute repetitive hypoxic mice model was developed. High-throughput microarray analysis was performed to explore the integrative alterations of gene expression in repetitive hypoxic mice. Data obtained was analyzed via multiple bioinformatics approaches to identify the hub genes, pathways and biological processes related to hypoxia preconditioning. The current study, for the first time, provides insights into the gene expression profiles in repetitive hypoxic mice...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29546239/divergence-in-problem-solving-skills-is-associated-with-differential-expression-of-glutamate-receptors-in-wild-finches
#5
Jean-Nicolas Audet, Lima Kayello, Simon Ducatez, Sara Perillo, Laure Cauchard, Jason T Howard, Lauren A O'Connell, Erich D Jarvis, Louis Lefebvre
Problem solving and innovation are key components of intelligence. We compare wild-caught individuals from two species that are close relatives of Darwin's finches, the innovative Loxigilla barbadensis , and its most closely related species in Barbados, the conservative Tiaris bicolor . We found an all-or-none difference in the problem-solving capacity of the two species. Brain RNA sequencing analyses revealed interspecific differences in genes related to neuronal and synaptic plasticity in the intrapallial neural populations (mesopallium and nidopallium), especially in the nidopallium caudolaterale, a structure functionally analogous to the mammalian prefrontal cortex...
March 2018: Science Advances
https://www.readbyqxmd.com/read/29511171/disease-associated-missense-mutations-in-glun2b-subunit-alter-nmda-receptor-ligand-binding-and-ion-channel-properties
#6
Laura Fedele, Joseph Newcombe, Maya Topf, Alasdair Gibb, Robert J Harvey, Trevor G Smart
Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg2+ block. In addition, we provide new views on Mg2+ and NMDA channel blocker binding sites...
March 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29230395/thc-treatment-alters-glutamate-receptor-gene-expression-in-human-stem-cell-derived-neurons
#7
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/29028947/dlx1-and-dlx2-promote-interneuron-gaba-synthesis-synaptogenesis-and-dendritogenesis
#8
Ramon Pla, Amelia Stanco, MacKenzie A Howard, Anna N Rubin, Daniel Vogt, Niall Mortimer, Inma Cobos, Gregory Brian Potter, Susan Lindtner, James D Price, Alex S Nord, Axel Visel, Christoph E Schreiner, Scott C Baraban, David H Rowitch, John L R Rubenstein
The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency...
September 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28993242/a-distinct-microrna-expression-profile-is-associated-with-%C3%AE-11-c-methyl-l-tryptophan-amt-pet-uptake-in-epileptogenic-cortical-tubers-resected-from-patients-with-tuberous-sclerosis-complex
#9
Shruti Bagla, Daniela Cukovic, Eishi Asano, Sandeep Sood, Aimee Luat, Harry T Chugani, Diane C Chugani, Alan A Dombkowski
Tuberous sclerosis complex (TSC) is characterized by hamartomatous lesions in various organs and arises due to mutations in the TSC1 or TSC2 genes. TSC mutations lead to a range of neurological manifestations including epilepsy, cognitive impairment, autism spectrum disorders (ASD), and brain lesions that include cortical tubers. There is evidence that seizures arise at or near cortical tubers, but it is unknown why some tubers are epileptogenic while others are not. We have previously reported increased tryptophan metabolism measured with α[11 C]-methyl-l-tryptophan (AMT) positron emission tomography (PET) in epileptogenic tubers in approximately two-thirds of patients with tuberous sclerosis and intractable epilepsy...
January 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/28921898/maternal-chronic-folate-supplementation-ameliorates-behavior-disorders-induced-by-prenatal-high-fat-diet-through-methylation-alteration-of-bdnf-and-grin2b-in-offspring-hippocampus
#10
Zhonghai Yan, Fei Jiao, Xiaoshuang Yan, Hailong Ou
SCOPE: Maternal consumption of a high-fat diet (HFD) during pregnancy increases the risk of behavioral problems. Folate plays an important role in neuroplasticity and the preservation of neuronal integrity. This study aims at determining the influence of diets supplemented with folate on offspring behavior, and the mechanisms involved. METHODS AND RESULTS: Female mice were fed a control diet, an HFD, control diet supplemented with folate, or an HFD supplemented with folate for 5 weeks before mating...
December 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28900078/-polymorphic-variants-of-glutamate-receptor-grik5-grin2b-and-serotonin-receptor-htr2a-genes-are-associated-with-chronic-obstructive-pulmonary-disease
#11
G F Korytina, L Z Akhmadishina, O V Kochetova, Y G Aznabaeva, Sh Z Zagidullin, T V Victorova
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system that affects primarily distal respiratory pathways and lung parenchyma. Smoking tobacco is a major risk factor for COPD. The relationship of HTR4 (rs3995090), HTR2A (rs6313), GRIK5 (rs8099939), GRIN2B (rs2268132), and CHRNB4 (rs1948) gene polymorphisms and COPD, as well as the contribution of these polymorphisms to the variations in quantitative characteristics that describe respiratory function, smoking behavior, and nicotine dependence was assessed in an ethnically homogeneous Tatar population...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28892521/a-systems-medicine-approach-for-finding-target-proteins-affecting-treatment-outcomes-in-patients-with-non-hodgkin-lymphoma
#12
Faezeh Ajorloo, Mohammad Vaezi, Alireza Saadat, Seyed Reza Safaee, Behrouz Gharib, Mostafa Ghanei, Seyed Davar Siadat, Farzam Vaziri, Abolfazl Fateh, Mehrdad Pazhouhandeh, Behrouz Vaziri, Reza Moazemi, Fereidoun Mahboudi, Fatemeh Rahimi Jamnani
Autoantibody profiling with a systems medicine approach can help identify critical dysregulated signaling pathways (SPs) in cancers. In this way, immunoglobulins G (IgG) purified from the serum samples of 92 healthy controls, 10 pre-treated (PR) non-Hodgkin lymphoma (NHL) patients, and 20 NHL patients who underwent chemotherapy (PS) were screened with a phage-displayed random peptide library. Protein-protein interaction networks of the PR and PS groups were analyzed and visualized by Gephi. The results indicated AXIN2, SENP2, TOP2A, FZD6, NLK, HDAC2, HDAC1, and EHMT2, in addition to CAMK2A, PLCG1, PLCG2, GRM5, GRIN2B, GRIN2D, CACNA2D3, and SPTAN1 as hubs in 11 and 7 modules of PR and PS networks, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28872674/the-methylazoxymethanol-acetate-rat-model-molecular-and-epigenetic-effect-in-the-developing-prefrontal-cortex-an-editorial-highlight-for-epigenetic-mechanisms-underlying-nmda-receptor-hypofunction-in-the-prefrontal-cortex-of-juvenile-animals-in-the-mam-model
#13
EDITORIAL
Xiyu Zhu, Felipe V Gomes, Anthony A Grace
This Editorial highlights an article by Gulchina and colleagues in the current issue of the Journal of Neurochemistry, in which the authors describe molecular and epigenetic changes in the developing prefrontal cortex of the rats exposed to methylazoxymethanol acetate (MAM). They found an NMDAR hypofunction present in the prefrontal cortex of juvenile MAM rats which was associated with abnormal epigenetic regulation of the Grin2b gene. These changes may be related to early cognitive impairments observed in MAM rats and schizophrenia patients...
November 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28839234/identification-of-ncan-as-a-candidate-gene-for-developmental-dyslexia
#14
Elisabet Einarsdottir, Myriam Peyrard-Janvid, Fahimeh Darki, Jetro J Tuulari, Harri Merisaari, Linnea Karlsson, Noora M Scheinin, Jani Saunavaara, Riitta Parkkola, Katri Kantojärvi, Antti-Jussi Ämmälä, Nancy Yiu-Lin Yu, Hans Matsson, Jaana Nopola-Hemmi, Hasse Karlsson, Tiina Paunio, Torkel Klingberg, Eira Leinonen, Juha Kere
A whole-genome linkage analysis in a Finnish pedigree of eight cases with developmental dyslexia (DD) revealed several regions shared by the affected individuals. Analysis of coding variants from two affected individuals identified rs146011974G > A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD in the pedigree. This variant prompted us to consider this gene as a putative candidate for DD. The RNA expression pattern of the NCAN gene in human tissues was highly correlated (R > 0...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837158/high-frequency-of-mosaic-pathogenic-variants-in-genes-causing-epilepsy-related-neurodevelopmental-disorders
#15
Mary Beth Stosser, Amanda S Lindy, Elizabeth Butler, Kyle Retterer, Caitlin M Piccirillo-Stosser, Gabriele Richard, Dianalee A McKnight
PurposeMosaicism probably represents an underreported cause of genetic disorders due to detection challenges during routine molecular diagnostics. The purpose of this study was to evaluate the frequency of mosaicism detected by next-generation sequencing in genes associated with epilepsy-related neurodevelopmental disorders.MethodsWe conducted a retrospective analysis of 893 probands with epilepsy who had a multigene epilepsy panel or whole-exome sequencing performed in a clinical diagnostic laboratory and were positive for a pathogenic or likely pathogenic variant in one of nine genes (CDKL5, GABRA1, GABRG2, GRIN2B, KCNQ2, MECP2, PCDH19, SCN1A, or SCN2A)...
August 24, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28745671/-a-role-of-interactions-between-n-methyl-d-aspartate-and-dopamine-receptors-in-facial-emotion-recognition-impairment-in-schizophrenia
#16
M V Alfimova, V E Golimbet, G I Korovaitseva, T V Lezheiko, D V Tikhonov, T K Ganisheva, N B Berezin, A A Snegireva, T K Shemiakina
AIM: To search for genetic mechanisms of facial emotion recognition (FER) impairment, one of the features of schizophrenia that affects social adaptation of patients. Based on the view implicating the interplay between dopaminergic and glutamatergic systems into the pathogenesis of schizophrenia, authors explored the interaction effects of the C366G polymorphism in the GRIN2B gene encoding NMDA receptor subunit NR2B with ANKK1/DRD2 Taq1A and 48-VNTR DRD4 polymorphisms on FER. MATERIAL AND METHODS: GRIN2B -DRD2 interaction effects were studied in a sample of 237 patients and 235 healthy controls, GRIN2B - DRD4 in 268 patients and 208 controls...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28734458/rett-like-severe-encephalopathy-caused-by-a-de-novo-grin2b-mutation-is-attenuated-by-d-serine-dietary-supplement
#17
David Soto, Mireia Olivella, Cristina Grau, Judith Armstrong, Clara Alcon, Xavier Gasull, Macarena Gómez de Salazar, Esther Gratacòs-Batlle, David Ramos-Vicente, Víctor Fernández-Dueñas, Francisco Ciruela, Àlex Bayés, Carlos Sindreu, Anna López-Sala, Àngels García-Cazorla, Xavier Altafaj
BACKGROUND: N-Methyl-D-aspartate receptors (NMDARs) play pivotal roles in synaptic development, plasticity, neural survival, and cognition. Despite recent reports describing the genetic association between de novo mutations of NMDAR subunits and severe psychiatric diseases, little is known about their pathogenic mechanisms and potential therapeutic interventions. Here we report a case study of a 4-year-old Rett-like patient with severe encephalopathy carrying a missense de novo mutation in GRIN2B(p...
January 15, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/28628228/epigenetic-mechanisms-underlying-nmda-receptor-hypofunction-in-the-prefrontal-cortex-of-juvenile-animals-in-the-mam-model-for-schizophrenia
#18
Yelena Gulchina, Song-Jun Xu, Melissa A Snyder, Felice Elefant, Wen-Jun Gao
Schizophrenia (SCZ) is characterized not only by psychosis, but also by working memory and executive functioning deficiencies, processes that rely on the prefrontal cortex (PFC). Because these cognitive impairments emerge prior to psychosis onset, we investigated synaptic function during development in the neurodevelopmental methylazoxymethanol (MAM) model for SCZ. Specifically, we hypothesize that N-methyl-D-aspartate receptor (NMDAR) hypofunction is attributable to reductions in the NR2B subunit through aberrant epigenetic regulation of gene expression, resulting in deficient synaptic physiology and PFC-dependent cognitive dysfunction, a hallmark of SCZ...
November 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28608743/obsessive-compulsive-disorder-which-genes-which-functions-which-pathways-an-integrated-holistic-view-regarding-ocd-and-its-complex-genetic-etiology
#19
Ali Bozorgmehr, Mohammad Ghadirivasfi, Esmaeil Shahsavand Ananloo
Obsessive-compulsive disorder (OCD) is characterized by recurrent obtrusive and repetitive acts typically occurred following anxiety. In the last two decades, studies done on the gene sequences, large-scale and point mutations and gene-gene, gene-environment and gene-drug interactions have led to the discovery of hundreds of genes associated with OCD. Although each gene in turn is a part of the etiology of this disorder; however, OCD, like other mental disorders is complex and a comprehensive and integrated view is necessary to understand its genetic basis...
June 13, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28594961/pirb-regulates-asymmetries-in-hippocampal-circuitry
#20
Hikari Ukai, Aiko Kawahara, Keiko Hirayama, Matthew Julian Case, Shotaro Aino, Masahiro Miyabe, Ken Wakita, Ryohei Oogi, Michiyo Kasayuki, Shihomi Kawashima, Shunichi Sugimoto, Kanako Chikamatsu, Noritaka Nitta, Tsuneyuki Koga, Ryuichi Shigemoto, Toshiyuki Takai, Isao Ito
Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B). By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI) proteins, do not exhibit circuit asymmetry...
2017: PloS One
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