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https://www.readbyqxmd.com/read/28213944/separation-of-hydroxynorketamine-stereoisomers-using-capillary-electrophoresis-with-sulfated-%C3%AE-cyclodextrin-and-highly-sulfated-%C3%AE-cyclodextrin
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28198441/pdi-regulates-seizure-activity-via-nmda-receptor-redox-in-rats
#12
Ji Yang Kim, Ah-Rhem Ko, Hye-Won Hyun, Su-Ji Min, Ji-Eun Kim
Redox modulation of cysteine residues is one of the post-translational modifications of N-methyl-D-aspartate receptor (NMDAR). Protein disulfide isomerases (PDI), an endoplasmic reticulum (ER) chaperone, plays a crucial role in catalyzing disulfide bond formation, reduction, and isomerization. In the present study, we found that PDI bound to NMDAR in the normal hippocampus, and that this binding was increased in chronic epileptic rats. In vitro thiol reductase assay revealed that PDI increased the amount of thiols on full-length recombinant NR1 protein...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198211/both-n-methyl-d-aspartate-and-non-n-methyl-d-aspartate-glutamate-receptors-in-the-bed-nucleus-of-the-stria-terminalis-modulate-the-cardiovascular-responses-to-acute-restraint-stress-in-rats
#13
Mariane B Adami, Lucas Barretto-de-Souza, Josiane O Duarte, Jeferson Almeida, Carlos C Crestani
The bed nucleus of the stria terminalis (BNST) is a forebrain structure that has been implicated on cardiovascular responses evoked by emotional stress. However, the local neurochemical mechanisms mediating the BNST control of stress responses are not fully described. In our study we investigated the involvement of glutamatergic neurotransmission within the BNST in cardiovascular changes evoked by acute restraint stress in rats. For this study, we investigated the effects of bilateral microinjections of selective antagonists of either N-methyl-D-aspartate (NMDA) or non-NMDA glutamate receptors into the BNST on the arterial pressure and heart rate increase and the decrease in tail skin temperature induced by acute restraint stress...
February 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28192149/serum-uric-acid-and-anti-n-methyl-d-aspartate-receptor-encephalitis
#14
Yaqing Shu, Yuge Wang, Tingting Lu, Rui Li, Xiaobo Sun, Jing Li, Yanyu Chang, Xueqiang Hu, Zhengqi Lu, Wei Qiu
BACKGROUND: Uric acid (UA) levels are associated with autoimmune and neurodegenerative disorders, but their relationship with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown. METHODS: UA levels were evaluated in 58 patients with anti-NMDAR encephalitis, and 58 age- and sex-matched healthy controls (CTLs). Follow-up evaluations of 30 out of the 58 patients with anti-NMDAR encephalitis were conducted 3 months after admission. Modified Rankin scale (mRS) scores and clinical and cerebrospinal fluid parameters were evaluated in all anti-NMDAR encephalitis patients...
February 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28187857/adaptive-and-behavioral-changes-in-kynurenine-3-monooxygenase-knockout-mice-relevance-to-psychotic-disorders
#15
Sophie Erhardt, Ana Pocivavsek, Mariaelena Repici, Xi-Cong Liu, Sophie Imbeault, Daniel C Maddison, Marian A R Thomas, Joshua L Smalley, Markus K Larsson, Paul J Muchowski, Flaviano Giorgini, Robert Schwarcz
BACKGROUND: Kynurenine 3-monooxygenase converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway-which is implicated as dysfunctional in various psychiatric disorders-toward enhanced synthesis of kynurenic acid, an antagonist of both α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors. Possibly as a result of reduced kynurenine 3-monooxygenase activity, elevated central nervous system levels of kynurenic acid have been found in patients with psychotic disorders, including schizophrenia...
December 16, 2016: Biological Psychiatry
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
#16
Thomas Boerner, Alexei 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...
February 10, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28186318/case-report-anti-n-methyl-d-aspartate-receptor-encephalitis-with-psychiatric-symptoms
#17
Ana Iglesias-Alonso, Celso Iglesias-García
No abstract text is available yet for this article.
January 2017: Actas Españolas de Psiquiatría
https://www.readbyqxmd.com/read/28186166/selective-molecular-impairment-of-spontaneous-neurotransmission-modulates-synaptic-efficacy
#18
Devon C Crawford, Denise M O Ramirez, Brent Trauterman, Lisa M Monteggia, Ege T Kavalali
Recent studies suggest that stimulus-evoked and spontaneous neurotransmitter release processes are mechanistically distinct. Here we targeted the non-canonical synaptic vesicle SNAREs Vps10p-tail-interactor-1a (vti1a) and vesicle-associated membrane protein 7 (VAMP7) to specifically inhibit spontaneous release events and probe whether these events signal independently of evoked release to the postsynaptic neuron. We found that loss of vti1a and VAMP7 impairs spontaneous high-frequency glutamate release and augments unitary event amplitudes by reducing postsynaptic eukaryotic elongation factor 2 kinase (eEF2K) activity subsequent to the reduction in N-methyl-D-aspartate receptor (NMDAR) activity...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28183990/human-dosimetry-of-the-nmda-receptor-ligand-11-c-gmom
#19
Jasper van der Aart, Thalia F van der Doef, Paul Horstman, Marc C Huisman, Robert C Schuit, Arthur van Lingen, Albert D Windhorst, Bart N M van Berckel, Adriaan A Lammertsma
The methylguanadine derivative [(11)C]GMOM has been used successfully to quantify N-methyl-D-aspartate (NMDA) receptor binding in humans. The purpose of the present study was to estimate the [(11)C]GMOM radiation dose in healthy humans. Methods: Following [(11)C]GMOM injection, three female and two male subjects underwent 10 consecutive whole body PET scans in approximately 77 minutes. 7 source organs were defined manually, scaled to a gender specific reference, and residence times were calculated for input into OLINDA/EXM software...
February 9, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28183578/a-case-of-central-diabetes-insipidus-after-ketamine-infusion-during-an-external-to-internal-carotid-artery-bypass
#20
Sharib Gaffar, Jonathan P Eskander, Burton D Beakley, Brian P McClure, Peter Amenta, Nakeisha Pierre
STUDY OBJECTIVE: We report the first teenage case of ketamine-induced transient central diabetes insipidus. CASE SUMMARY: The patient was an 18-year-old woman with moyamoya disease undergoing an external carotid to internal carotid bypass and given a low-dose ketamine infusion. After approximately 2 hours in the supine position, with 0.5 Minimum Alveolar Concentration (MAC) of sevoflurane, a propofol infusion at 50 μg/kg/min, a remifentanil infusion at 0.5 μg/kg/min, and a ketamine infusion at a dose of 10 μg/kg/min, this patient had an excessive urine output...
February 2017: Journal of Clinical Anesthesia
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