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https://www.readbyqxmd.com/read/28228639/grin1-mutation-associated-with-intellectual-disability-alters-nmda-receptor-trafficking-and-function
#1
Wenjuan Chen, Christine Shieh, Sharon A Swanger, Anel Tankovic, Margaret Au, Marianne McGuire, Michele Tagliati, John M Graham, Suneeta Madan-Khetarpal, Stephen F Traynelis, Hongjie Yuan, Tyler Mark Pierson
N-methyl-d-aspartate receptors (NMDARs) play important roles in brain development and neurological disease. We report two individuals with similar dominant de novo GRIN1 mutations (c.1858 G>A and c.1858 G>C; both p.G620R). Both individuals presented at birth with developmental delay and hypotonia associated with behavioral abnormalities and stereotypical movements. Recombinant NMDARs containing the mutant GluN1-G620R together with either GluN2A or GluN2B were evaluated for changes in their trafficking to the plasma membrane and their electrophysiological properties...
February 23, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28228087/beyond-ketamine-new-approaches-to-the-development-of-safer-antidepressants
#2
Shigeyuki Chaki
Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention...
February 20, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28225480/nmda-receptor-subunit-and-camkii-changes-in-rat-hippocampus-by-congenital-hcmv-infection-a-mechanism-for-learning-and-memory-impairment
#3
De Wu, Li Yang, Xiaosong Bu, Jiulai Tang, Xiaocheng Fan
The aim of this study was to investigate the effects of congenital human cytomegalovirus infection on the expression levels of N-methyl-D-aspartate receptors (NRs) and Ca/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal neurons of neonatal Sprague-Dawley (SD) rats. Pregnant SD rats were divided into an experimental group and a control group (n=10 in each group). Spatial learning and memory of the offspring of SD rats were evaluated using the Morris water-maze test. Pathological studies of hippocampus sections were carried out...
February 20, 2017: Neuroreport
https://www.readbyqxmd.com/read/28225161/treatment-of-experimental-status-epilepticus-with-synergistic-drug-combinations
#4
Jerome Niquet, Roger Baldwin, Lucie Suchomelova, Lucille Lumley, Roland Eavey, Claude G Wasterlain
During status epilepticus (SE), synaptic γ-aminobutyric acid A receptors (GABAA Rs) become internalized and inactive, whereas spare N-methyl-d-aspartate receptors (NMDARs) assemble, move to the membrane, and become synaptically active. When treatment of SE is delayed, the number of synaptic GABAA Rs is drastically reduced, and a GABAA agonist cannot fully restore inhibition. We used a combination of low-dose diazepam (to stimulate the remaining GABAA Rs), ketamine (to mitigate the effect of the NMDAR increase), and valproate (to enhance inhibition at a nonbenzodiazepine site) to treat seizures in a model of severe cholinergic SE...
February 22, 2017: Epilepsia
https://www.readbyqxmd.com/read/28223913/neuromorphic-implementation-of-attractor-dynamics-in-a-two-variable-winner-take-all-circuit-with-nmdars-a-simulation-study
#5
Hongzhi You, Da-Hui Wang
Neural networks configured with winner-take-all (WTA) competition and N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic dynamics are endowed with various dynamic characteristics of attractors underlying many cognitive functions. This paper presents a novel method for neuromorphic implementation of a two-variable WTA circuit with NMDARs aimed at implementing decision-making, working memory and hysteresis in visual perceptions. The method proposed is a dynamical system approach of circuit synthesis based on a biophysically plausible WTA model...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28223808/n-methyl-d-aspartate-receptor-antibody-could-be-a-cause-of-catatonic-symptoms-in-psychiatric-patients-case-reports-and-methods-for-detection
#6
Ko Tsutsui, Takashi Kanbayashi, Manabu Takaki, Yuki Omori, Yumiko Imai, Seiji Nishino, Keiko Tanaka, Tetsuo Shimizu
The symptoms of catatonia have been reported to be similar to the initial symptoms of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Subsequently, this autoimmune limbic encephalitis has been noticed by many psychiatrists. For a differential diagnosis of catatonic state, it is important to detect anti-NMDAR encephalitis. This encephalitis is expected to be in remission by early detection and treatment. We should be more cautious about catatonic symptoms of schizophrenia. When a patient is suspected of having encephalitis, we should screen for anti-NMDAR antibodies in cerebrospinal fluid samples using a cell-based assay...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28222697/magnesium-sulphate-attenuate-remifentanil-induced-postoperative-hyperalgesia-via-regulating-tyrosine-phosphorylation-of-the-nr2b-subunit-of-the-nmda-receptor-in-the-spinal-cord
#7
Jiehao Sun, Hai Lin, Guodong He, Wendong Lin, Jianping Yang
BACKGROUND: Remifentanil induced hyperalgesia (RIH) is characterized by stimulation evoked pain including allodynia and thermal hyperalgesia after remifentanil infusion. N-methyl-D-aspartate (NMDA) receptor was reported to be involved in the progress of RIH. We hypothesized that intrathecal MgSO4 could relieve hyperalgesia after remifentanil infusion via regulating phosphorylation of NMDA receptor NR2B subunit activity in this study. METHODS: Thirty two rats were randomly allocated into control group, model of RIH group, RIH plus 100ug MgSO4 group, RIH plus 300ug MgSO4 group...
February 21, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28222314/systematic-variation-of-the-benzenesulfonamide-part-of-the-glun2a-selective-nmda-receptor-antagonist-tcn-201
#8
Sebastian L Müller, Julian A Schreiber, Dirk Schepmann, Nathalie Strutz-Seebohm, Guiscard Seebohm, Bernhard Wünsch
GluN2A subunit containing N-methyl-d-aspartate receptors (NMDARs) are highly involved in various physiological processes in the central nervous system, but also in some diseases, such as anxiety, depression and schizophrenia. However, the role of GluN2A subunit containing NMDARs in pathological processes is not exactly elucidated. In order to obtain potent and selective inhibitors of GluN2A subunit containing NMDARs, the selective negative allosteric modulator 2 was systematically modified at the benzenesulfonamide part...
February 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28218498/optimization-of-bicyclic-lactam-derivatives-as-nmda-receptor-antagonists
#9
Margarida Espadinha, Jorge Dourado, Rocio Lajarin-Cuesta, Clara Herrera-Arozamena, Lidia Gonçalves, Maria Isabel Rodríguez-Franco, Cristobal de Los Rios, Maria M M Santos
N-Methyl-D-aspartate (NMDA) receptors are fundamental for the normal function of the central nerve system, and play an important role in memory and learning. An overactivation of these receptors will lead to neuronal loss associated with major neurological disorders, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and epilepsy. Herein, twenty two novel enantiopure bicyclic lactams were designed, synthesized, and evaluated as NMDA receptor antagonists. Most of the new compounds displayed NMDA receptor antagonism and, the most promising compound showed IC50 value in the same order of magnitude of memantine, a NMDA receptor antagonist used in the clinic for the treatment of Alzheimer's disease...
February 20, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28213944/separation-of-hydroxynorketamine-stereoisomers-using-capillary-electrophoresis-with-sulfated-%C3%AE-cyclodextrin-and-highly-sulfated-%C3%AE-cyclodextrin
#10
Friederike A Sandbaumhüter, Regula Theurillat, Wolfgang Thormann
The racemic N-methyl-d-aspartate receptor antagonist ketamine is used in anesthesia, analgesia and the treatment of depressive disorders. It is known that interactions of hydroxylated norketamine metabolites and 5,6-dehydronorketamine (DHNK) with the α7 -nicotinic acetylcholine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are responsible for the antidepressive effects. Ketamine and its first metabolite norketamine are not active on these receptors. As stereoselectivity plays a role in ketamine metabolism, a cationic capillary electrophoresis based method capable of resolving and analyzing the stereoisomers of four hydroxylated norketamine metabolites, norketamine and DHNK was developed...
February 18, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28213064/juvenile-treatment-with-a-novel-mglur2-agonist-mglur3-antagonist-compound-ly395756-reverses-learning-deficits-and-cognitive-flexibility-impairments-in-adults-in-a-neurodevelopmental-model-of-schizophrenia
#11
Meng-Lin Li, Yelena Gulchina, Sarah A Monaco, Bo Xing, Brielle R Ferguson, Yan-Chun Li, Feng Li, Xi-Quan Hu, Wen-Jun Gao
Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms...
February 14, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28212832/motor-dysfunction-and-alterations-in-glutathione-concentration-cholinesterase-activity-and-bdnf-expression-in-substantia-nigra-pars-compacta-in-rats-with-pedunculopontine-lesion
#12
Lisette Blanco-Lezcano, Javier Jimenez-Martin, Mei-Li Díaz-Hung, Esteban Alberti-Amador, Maylin Wong-Guerra, Ma Elena González-Fraguela, Bárbara Estupiñán-Díaz, Teresa Serrano-Sánchez, Liliana Francis-Turner, Susana Delgado-Ocaña, Yanier Núñez-Figueredo, Yamilé Vega-Hurtado, Isabel Fernández-Jiménez
Pedunculopontine nucleus (PPN) has been considered a critically important region in the regulation of some of the physiological functions that fail during the progression of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN [through the injection of N-methyl-D-aspartate (NMDA) solution (concentration: 0.1 M; volume: 0.5 µL)] in motor execution and gait disorders and the changes in cellular and molecular indicators in rat nigral tissue were evaluated. The motor execution was assessed using the beam test (BT) and the gait disorders by footprint test...
February 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/28211672/proteomic-analysis-of-post-synaptic-protein-complexes-underlying-neuronal-plasticity
#13
Anthony J Baucum
Normal neuronal communication and synaptic plasticity at glutamatergic synapses requires dynamic regulation of postsynaptic molecules. Protein expression and protein post-translational modifications regulate protein interactions that underlie this organization. In this review, we highlight data obtained over the last 20 years that have used qualitative and quantitative proteomics-based approaches to identify postsynaptic protein complexes. Herein, we describe how these proteomics studies have helped lay the foundation for understanding synaptic physiology and perturbations in synaptic signaling observed in different pathologies...
February 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28210722/synthesis-radio-synthesis-and-in-vitro-evaluation-of-terminally-fluorinated-derivatives-of-hu-210-and-hu-211-as-novel-candidate-pet-tracers
#14
Chiara Zanato, Alessia Pelagalli, Katie F M Marwick, Monica Piras, Sergio Dall'Angelo, Andrea Spinaci, Roger G Pertwee, David J A Wyllie, Giles E Hardingham, Matteo Zanda
We report the synthesis of terminally fluorinated HU-210 and HU-211 analogues (HU-210F and HU-211F, respectively) and their biological evaluation as ligands of cannabinoid receptors (CB1 and CB2) and N-methyl d-aspartate receptor (NMDAR). [(18)F]-labelled HU-210F was radiosynthesised from the bromo-substituted precursor. In vitro assays showed that both HU-210F and HU-211F retain the potent pharmacological profile of HU-210 and HU-211, suggesting that [(18)F]-radiolabelled HU-210F and HU-211F could have potential as PET tracers for in vivo imaging...
February 17, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28209776/distance-dependent-gradient-in-nmdar-driven-spine-calcium-signals-along-tapering-dendrites
#15
Alison S Walker, Guilherme Neves, Federico Grillo, Rachel E Jackson, Mark Rigby, Cian O'Donnell, Andrew S Lowe, Gema Vizcay-Barrena, Roland A Fleck, Juan Burrone
Neurons receive a multitude of synaptic inputs along their dendritic arbor, but how this highly heterogeneous population of synaptic compartments is spatially organized remains unclear. By measuring N-methyl-d-aspartic acid receptor (NMDAR)-driven calcium responses in single spines, we provide a spatial map of synaptic calcium signals along dendritic arbors of hippocampal neurons and relate this to measures of synapse structure. We find that quantal NMDAR calcium signals increase in amplitude as they approach a thinning dendritic tip end...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28209726/therapeutic-targeting-of-the-pathological-triad-of-extrasynaptic-nmda-receptor-signaling-in-neurodegenerations
#16
REVIEW
Hilmar Bading
Activation of extrasynaptic N-methyl-d-aspartate (NMDA) receptors causes neurodegeneration and cell death. The disease mechanism involves a pathological triad consisting of mitochondrial dysfunction, loss of integrity of neuronal structures and connectivity, and disruption of excitation-transcription coupling caused by CREB (cyclic adenosine monophosphate-responsive element-binding protein) shut-off and nuclear accumulation of class IIa histone deacetylases. Interdependency within the triad fuels an accelerating disease progression that culminates in failure of mitochondrial energy production and cell loss...
February 16, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28204809/ketamine-suppresses-the-substance-p-induced-production-of-il-6-and-il-8-by-human-u373mg-glioblastoma-astrocytoma-cells
#17
Keisuke Yamaguchi, Seiichiro Kumakura, Taisuke Murakami, Akimasa Someya, Eiichi Inada, Isao Nagaoka
The neuropeptide substance P (SP) is an important mediator of neurogenic inflammation within the central and peripheral nervous systems. SP has been shown to induce the expression of pro-inflammatory cytokines implicated in the pathogenesis of several disorders of the human brain via the neurokinin-1 receptor (NK-1R). Ketamine, an intravenous anesthetic agent, functions as a competitive antagonist of the excitatory neurotransmission N-methyl-D‑aspartate (NMDA) receptor, and also antagonizes the NK-1R by interfering with the binding of SP...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202572/differential-regulation-of-nmda-receptors-by-d-serine-and-glycine-in-mammalian-spinal-locomotor-networks
#18
David Acton, Gareth Brian Miles
Activation of N-methyl-D-aspartate receptors (NMDARs) requires the binding of a co-agonist, either D-serine or glycine, in addition to glutamate. Changes in occupancy of the co-agonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR co-agonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by D(-)-2-amino-5-phosphonopentanoic acid (D-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28202296/psychosis-in-the-ed-a-case-of-nmda-receptor-antibody-encephalitis
#19
Joseph Fisher, Clifford Ellingson, Noah Tolby
Anti-N-methyl-d-aspartate antibody receptor (NMDAR) encephalitis is a newly recognized disease increasing in diagnostic frequency. A 27-year-old female presented with symptoms of oral dyskinesia, tachycardia, and altered mental status following a three-month history of depression, lethargy, catatonia, and auditory hallucinations. We utilized our facilities neurology and psychiatry consult services, performed a lumbar puncture (LP), and requested NMDAR antibody titers. Following admission the Anti-NMDAR antibody titer was elevated warranting treatment with intravenous immunoglobulin (IVIG), corticosteroids, and later rituximab...
February 6, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28199666/the-role-of-dopamine-d1-and-d3-receptors-in-n-methyl-d-aspartate-nmda-glycineb-site-regulated-complex-cognitive-behaviors-following-repeated-morphine-administration
#20
Yunpeng Wang, Fangyuan Yin, Hao Guo, Jing Zhang, Peng Yan, Jianghua Lai
No abstract text is available yet for this article.
February 11, 2017: International Journal of Neuropsychopharmacology
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