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GluN2A

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https://www.readbyqxmd.com/read/29127002/post-acquisition-hippocampal-blockade-of-the-nmda-receptor-subunit-glun2a-but-not-glun2b-sustains-spatial-reference-memory-retention
#1
Keisuke Shinohara, Toshimichi Hata
While it has been shown that the blockade of N-methyl-d-aspartate type glutamate receptors (NMDARs) impairs memory acquisition, recent studies have reported that the post-acquisition administration of NMDAR antagonists suppresses spatial memory decay. These findings suggest that NMDARs are important not only for the acquisition of new memories but also for the decay of previously acquired memories. The present study investigated the contributions of specific NMDAR subunits to spatial memory decay using NVP-AAM077 (NVP), an NMDAR antagonist that preferentially binds to GluN2A subunits, and the selective GluN2B blocker Ro 25-6981 (Ro)...
November 7, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29101031/a-deficiency-of-the-glun2c-subunit-of-the-n-methyl-d-aspartate-receptor-is-neuroprotective-in-a-mouse-model-of-ischemic-stroke
#2
Adam Holmes, Ning Zhou, Deborah L Donahue, Rashna Balsara, Francis J Castellino
The N-methyl-d-aspartate receptor (NMDAR) ion channel plays a pivotal role in the pathology of ischemic stroke. The functional receptor consists of two GluN1 subunits (a-h) and two GluN2 subunits (A/B/C/D), the expression of which are spatially and temporally regulated in pathological and physiological conditions. While the role of the GluN2A and GluN2B subunit in ischemic stroke has been well developed, the role of the GluN2C subunit in ischemia is not well understood. Following middle carotid artery occlusion (MCAO), GluN2C(-/-) male mice displayed similar volumes of infarct as wild-type (WT) mice...
October 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29073350/understanding-the-antibody-repertoire-in-neuropsychiatric-systemic-lupus-erythematosus-and-neuromyelitis-optica-spectrum-disorders-do-they-share-common-targets
#3
Simone Mader, Venkatesh Jeganathan, Yoshiyuki Arinuma, Yuichiro Fujieda, Irena Dujmovic, Jelena Drulovic, Yuka Shimizu, Yuko Sakuma, Joel N H Stern, Cynthia Aranow, Meggan Mackay, Shinsuke Yasuda, Tatsuya Atsumi, Shunsei Hirohata, Betty Diamond
OBJECTIVE: DWEYS-IgG cross-reactive with DNA and the N-methyl-D-aspartate receptor subunits GluN2A/GluN2B has been associated with neuropsychiatric systemic lupus erythematosus (NPSLE). DWEYS-IgG has not been investigated in demyelinating NPSLE (dNPSLE) or in another demyelinating disorder, Neuromyelitis Optica Spectrum Disorder (NMOSD), which is also a disease of young women and associated with aquaporin-4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibodies. We investigated the frequency of these brain-reactive antibodies in NPSLE, dNPSLE and NMOSD...
October 26, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29052618/a-role-for-prefrontal-cortical-nmda-receptors-in-murine-alcohol-heightened-aggression
#4
Emily L Newman, Miho Terunuma, Tiffany Wang, Nishani Hewage, Matthew B Bicakci, Stephen J Moss, Joseph F DeBold, Klaus A Miczek
Alcohol is associated with nearly half of all violent crimes committed in the United States; yet, a potential neural basis for this type of pathological aggression remains elusive. Alcohol may act on NMDA receptors (NMDARs) within cortical circuits to impede processing and to promote aggression. Here, male mice were characterized as alcohol-heightened (AHAs) or alcohol non-heightened aggressors (ANAs) during resident-intruder confrontations after self-administering 1.0 g/kg alcohol (6% w/v) or water. Alcohol produced a pathological-like pattern of aggression in AHAs; these mice shifted their bites to more vulnerable locations on the body of a submissive animal, including the anterior back and ventrum after consuming alcohol...
October 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29043770/a-novel-negative-allosteric-modulator-selective-for-glun2c-2d-containing-nmda-receptors-inhibits-synaptic-transmission-in-hippocampal-interneurons
#5
Sharon A Swanger, Katie M Vance, Timothy M Acker, Sommer S Zimmerman, John O DiRaddo, Scott J Myers, Christoffer Bundgaard, Cara A Mosley, Samantha L Summer, David S Menaldino, Henrik S Jensen, Dennis C Liotta, Stephen F Traynelis
N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 and two GluN2 subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional properties and gene expression patterns, which contribute to diverse functional roles for NMDARs in the brain. Here, we present a series of GluN2C/2D-selective negative allosteric modulators built around a N-aryl benzamide (NAB) core...
November 2, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29035834/synergistic-effect-of-mild-hypothermia-and-the-notch-inhibitor-dapt-against-post-stroke-seizures
#6
Guo-Shuai Yang, Xiao-Yan Zhou, Xue-Fang An, Xuan-Jun Liu, Yan-Jun Zhang, Dan Yu
Seizure is a serious complication of stroke, indicating poor prognosis. Notch signaling is associated with neuronal activity. Inhibition of Notch signaling suppresses seizure activity induced by kainic acid. The present study investigated the effect of the Notch inhibitor, DAPT, alone or in combination with mild hypothermia, on post-stroke seizures. A global cerebral ischemia (GCI) model was performed in Sprague Dawley (SD) male rats. Seizure activity was evaluated by the frequency of seizure attacks, seizure severity scores, and seizure discharges...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29024713/a-lack-of-glun2a-containing-nmda-receptors-confers-a-vulnerability-to-redox-dysregulation-consequences-on-parvalbumin-interneurons-and-their-perineuronal-nets
#7
Romain Cardis, Jan-Harry Cabungcal, Daniella Dwir, Kim Q Do, Pascal Steullet
The GluN2A subunit of NMDA receptors (NMDARs) plays a critical role during postnatal brain development as its expression increases while Glun2B expression decreases. Mutations and polymorphisms in GRIN2A gene, coding for GluN2A, are linked to developmental brain disorders such as mental retardation, epilepsy, schizophrenia. Published data suggest that GluN2A is involved in maturation and phenotypic maintenance of parvalbumin interneurons (PVIs), and these interneurons suffer from a deficient glutamatergic neurotransmission via GluN2A-containing NMDARs in schizophrenia...
October 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28986871/selective-cell-surface-expression-of-triheteromeric-nmda-receptors
#8
Feng Yi, Stephen F Traynelis, Kasper B Hansen
The NMDA-type ionotropic glutamate receptors play pivotal roles in many brain functions, but are also involved in numerous brain disorders. Seven NMDA receptor subunits exist (GluN1, GluN2A-D, and GluN3A-B) that assemble into a diverse array of tetrameric receptor subtypes with distinct functional properties and physiological roles. Most NMDA receptors are composed of two GluN1 and two GluN2 subunits, which can assemble into four diheteromeric receptor subtypes composed of GluN1 and one type of GluN2 subunit (e...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986869/magnetofection%C3%A2-of-nmda-receptor-subunits-glun1-and-glun2a-expression-vectors-in-non-neuronal-host-cells
#9
Nadine Bruneau, Pierre Szepetowski
The functional study of reconstituted NMDA receptors (NMDARs) in host cells requires that the corresponding vectors for the expression of the NMDAR subunits are co-transfected with high efficiency. Magnetofection™ is a technology used to deliver nucleic acids to cells. It is driven and site-specifically guided by the attractive forces of magnetic fields acting on magnetic nanoparticles that are associated with nucleic acid vectors. In magnetofection™, cationic lipids form self-assembled complexes with the nucleic acid vectors of interest...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986867/genetic-and-functional-analysis-of-grin2a-in-tumor-samples
#10
Todd D Prickett, Jared J Gartner, Yardena Samuels
Ionotropic glutamate receptors (iGluRs) are large integral membrane multi-protein complexes that create ion channels in plasma membranes. Upon binding of receptor specific ligands (e.g., glutamate), increased efflux or influx of mono- or divalent cations (e.g., Ca(2+)) promotes synaptic transmission, cellular migration, and survival. Three classes of iGluRs were originally defined after their respective agonists: AMPA, kainate, and NMDA receptors (NMDARs). Recently, we examined iGluR families at the genetic level using Next-Generation Sequencing (NGS) (whole-exome sequencing (WES)) and discovered a high prevalence of somatic mutations within the gene for one of the NMDAR subunits, GRIN2A, specifically in malignant melanoma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28981594/neuron-targeted-caveolin-1-promotes-ultrastructural-and-functional-hippocampal-synaptic-plasticity
#11
Junji Egawa, Alice Zemljic-Harpf, Chitra D Mandyam, Ingrid R Niesman, Larisa V Lysenko, Alexander M Kleschevnikov, David M Roth, Hemal H Patel, Piyush M Patel, Brian P Head
A delicate interneuronal communication between pre- and postsynaptic membranes is critical for synaptic plasticity and the formation of memory. Evidence shows that membrane/lipid rafts (MLRs), plasma membrane microdomains enriched in cholesterol and sphingolipids, organize presynaptic proteins and postsynaptic receptors necessary for synaptic formation and signaling. MLRs establish a cell polarity that facilitates transduction of extracellular cues to the intracellular environment. Here we show that neuron-targeted overexpression of an MLR protein, caveolin-1 (SynCav1), in the adult mouse hippocampus increased the number of presynaptic vesicles per bouton, total excitatory type I glutamatergic synapses, number of same-dendrite multiple-synapse boutons, increased myelination, increased long-term potentiation, and increased MLR-localized N-methyl-d-aspartate receptor subunits (GluN1, GluN2A, and GluN2B)...
July 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28957809/geniposide-attenuates-post-ischaemic-neurovascular-damage-via-glun2a-akt-erk-dependent-mechanism
#12
Baosheng Huang, Panhong Chen, Lei Huang, Shuai Li, Ronglan Zhu, Tao Sheng, Wan Yu, Zheng Chen, Tianlu Wang
BACKGROUND/AIMS: Calcium-permeable ionotropic NMDAR-mediated hyperactivity is regarded as the critical factor in modulating the development of ischaemic stroke. Recently, there has been increasing interest in preventing post-stroke neuronal death by focusing on intervening in the function of subpopulations of NMDARs and their downstream signalling. Geniposide, an iridoid glycoside, has been found to have cytoprotective functions in various conditions. However, it is still unclear whether and how geniposide affects neuronal insult under experimental stroke...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28936771/functional-investigation-of-a-grin2a-variant-associated-with-rolandic-epilepsy
#13
Xing-Xing Xu, Xiao-Rong Liu, Cui-Ying Fan, Jin-Xing Lai, Yi-Wu Shi, Wei Yang, Tao Su, Jun-Yu Xu, Jian-Hong Luo, Wei-Ping Liao
N-methyl-D-aspartate receptors (NMDARs), a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2A (a gene encoding the NMDAR GluN2A subunit) mutations in patients with epilepsy. Phenotypes of GRIN2A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2A mutation (c.1341T>A, p.N447K) from a boy with Rolandic epilepsy by whole-exome sequencing...
September 21, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28916251/mk-801-but-not-naloxone-attenuates-high-dose-dextromethorphan-induced-convulsive-behavior-possible-involvement-of-the-glun2b-receptor
#14
Hai-Quyen Tran, Yoon Hee Chung, Eun-Joo Shin, The-Vinh Tran, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity...
November 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28912687/alterations-in-properties-of-glutamatergic-transmission-in-the-temporal-cortex-and-hippocampus-following-pilocarpine-induced-acute-seizures-in-wistar-rats
#15
Dmitry V Amakhin, Sergey L Malkin, Julia L Ergina, Kirill A Kryukov, Ekaterina A Veniaminova, Olga E Zubareva, Aleksey V Zaitsev
Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in humans, and is often developed after an initial precipitating brain injury. This form of epilepsy is frequently resistant to pharmacological treatment; therefore, the prevention of TLE is the prospective approach to TLE therapy. The lithium-pilocarpine model in rats replicates some of the main features of TLE in human, including the pathogenic mechanisms of cell damage and epileptogenesis after a primary brain injury. In the present study, we investigated changes in the properties of glutamatergic transmission during the first 3 days after pilocarpine-induced acute seizures in Wistar rats (PILO-rats)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28887453/hyaluronic-acid-based-extracellular-matrix-regulates-surface-expression-of-glun2b-containing-nmda-receptors
#16
Barbara Schweitzer, Jeet Singh, Anna Fejtova, Laurent Groc, Martin Heine, Renato Frischknecht
Cortical areas of the juvenile rodent brain display a high degree of structural and functional plasticity, which disappears later in development. Coincident with the decline of plasticity 1) the hyaluronic acid-based extracellular matrix (ECM) of the brain, which stabilizes synapses and neuronal circuit is formed and 2) N-methyl-D-aspartate subtype of ionotropic glutamate receptors (NMDARs) implied in synaptic plasticity switch from mainly GluN2B to GluN2A subunit-containing receptors. Here we tested the hypothesis that ECM influences the NMDAR subunit composition in dissociated neuronal cultures...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855140/prenatal-stress-induced-gender-specific-alterations-of-n-methyl-d-aspartate-receptor-subunit-expression-and-response-to-a%C3%AE-in-offspring-hippocampal-cells
#17
Yuan Fang, Hui Li, Lirong Chang, Yizhi Song, Longhui Ma, Liying Lu, Zunshu Du, Yan Li, Jinping Liu, Yan Wu
Prenatal stress (PS) is one of adverse life events during pregnancy, which may increase vulnerability to cognitive impairment in adult offspring. Aβ synaptotoxicity is one important pathological factor for cognitive impairment, and PS-induced cognitive disorder is closely associated with N-Methyl-d-Aspartate receptor (NMDAR), which acts as a key mediator of Aβ synaptotoxicity. In the present study, we tried to explore whether PS affects offspring's Aβ levels and NMDAR subunit expression in a gender-specific manner in hippocampal CA and DG subregions, and whether PS affects synaptic proteins and NMDAR subunit expression in cultured offspring hippocampal cells exposed to Aβ...
January 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28800762/the-novel-cannabinoid-receptor-gpr55-mediates-anxiolytic-like-effects-in-the-medial-orbital-cortex-of-mice-with-acute-stress
#18
Qi-Xin Shi, Liu-Kun Yang, Wen-Long Shi, Lu Wang, Shi-Meng Zhou, Shao-Yu Guan, Ming-Gao Zhao, Qi Yang
The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid receptor, whose exact role in anxiety remains unknown. The present study was conducted to explore the possible mechanisms by which GPR55 regulates anxiety and to evaluate the effectiveness of O-1602 in the treatment of anxiety-like symptoms. Mice were exposed to two types of acute stressors: restraint and forced swimming. Anxiety behavior was evaluated using the elevated plus maze and the open field test. We found that O-1602 alleviated anxiety-like behavior in acutely stressed mice...
August 11, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28761055/a-single-channel-mechanism-for-pharmacological-potentiation-of-glun1-glun2a-nmda-receptors
#19
Divyan A Chopra, Kiran Sapkota, Mark W Irvine, Guangyu Fang, David E Jane, Daniel T Monaghan, Shashank M Dravid
NMDA receptors (NMDARs) contribute to several neuropathological processes. Novel positive allosteric modulators (PAMs) of NMDARs have recently been identified but their effects on NMDAR gating remain largely unknown. To this end, we tested the effect of a newly developed molecule UBP684 on GluN1/GluN2A receptors. We found that UBP684 potentiated the whole-cell currents observed under perforated-patch conditions and slowed receptor deactivation. At the single channel level, UBP684 produced a dramatic reduction in long shut times and a robust increase in mean open time...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760974/structural-basis-of-subunit-selectivity-for-competitive-nmda-receptor-antagonists-with-preference-for-glun2a-over-glun2b-subunits
#20
Genevieve E Lind, Tung-Chung Mou, Lucia Tamborini, Martin G Pomper, Carlo De Micheli, Paola Conti, Andrea Pinto, Kasper B Hansen
NMDA-type glutamate receptors are ligand-gated ion channels that contribute to excitatory neurotransmission in the central nervous system (CNS). Most NMDA receptors comprise two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (GluN2A-D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]-4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive GluN2 antagonists, of which ST3 has a binding affinity of 52 nM at GluN1/2A and 782 nM at GluN1/2B receptors. This 15-fold preference of ST3 for GluN1/2A over GluN1/2B is improved compared with NVP-AAM077, a widely used GluN2A-selective antagonist, which we show has 11-fold preference for GluN1/2A over GluN1/2B...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
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