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N-methyl-D-aspartate

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https://www.readbyqxmd.com/read/29679291/role-of-phosphatidylinositol-3-kinase-pathway-in-nmda-preconditioning-different-mechanisms-for-seizures-and-hippocampal-neuronal-degeneration-induced-by-quinolinic-acid
#1
Leandra C Constantino, Luisa B Binder, Samuel Vandresen-Filho, Giordano G Viola, Fabiana K Ludka, Mark W Lopes, Rodrigo B Leal, Carla I Tasca
N-methyl D-aspartate (NMDA) preconditioning is evoked by the administration of a subtoxic dose of NMDA and is protective against neuronal excitotoxicity. This effect may involve a diversity of targets and cell signaling cascades associated to neuroprotection. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases (MAPKs) such as extracellular regulated protein kinase 1/2 (ERK1/2) and p38MAPK pathways play a major role in neuroprotective mechanisms. However, their involvement in NMDA preconditioning was not yet fully investigated...
April 20, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29679289/cross-state-dependency-of-learning-between-tramadol-and-mk-801-in-the-mouse-dorsal-hippocampus-involvement-of-nitric-oxide-no-signaling-pathway
#2
Majid Jafari-Sabet, Shiva Amiri, Ramin Ataee
RATIONALE: Tramadol, an atypical μ-opioid receptor agonist, as a psychoactive drug, is frequently abused by human beings. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help prevent drug addiction and relapse. Previous study revealed that dorsal hippocampus (CA1) plays a crucial role in the retrieval of tramadol-associated memory and that its role depends on the expression of CA1 N-methyl-D-aspartate (NMDA) receptors (Jafari-Sabet et al...
April 21, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29677389/population-pharmacokinetics-of-intramuscular-and-intravenous-ketamine-in-children
#3
Christoph P Hornik, Daniel Gonzalez, John van den Anker, Andrew M Atz, Ram Yogev, Brenda B Poindexter, Kee Chong Ng, Paula Delmore, Barrie L Harper, Chiara Melloni, Andrew Lewandowski, Casey Gelber, Michael Cohen-Wolkowiez, Jan Hau Lee
Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascular access is limited. Pharmacokinetic (PK) data in children are sparse, and the bioavailability of intramuscular ketamine in children is unknown. We performed 2 prospective PK studies of ketamine in children receiving either intramuscular or intravenous ketamine and combined the data to develop a pediatric population PK model using nonlinear mixed-effects methods...
April 20, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29675578/the-parkinson-s-disease-linked-protein-dj-1-associates-with-cytoplasmic-mrnp-granules-during-stress-and-neurodegeneration
#4
Mariaelena Repici, Mahdieh Hassanjani, Daniel C Maddison, Pedro Garção, Sara Cimini, Bhavini Patel, Éva M Szegö, Kornelis R Straatman, Kathryn S Lilley, Tiziana Borsello, Tiago F Outeiro, Lia Panman, Flaviano Giorgini
Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). DJ-1 plays a role in protection from oxidative stress, but how it functions as an "upstream" oxidative stress sensor and whether this relates to PD is still unclear. Intriguingly, DJ-1 may act as an RNA binding protein associating with specific mRNA transcripts in the human brain. Moreover, we previously reported that the yeast DJ-1 homolog Hsp31 localizes to stress granules (SGs) after glucose starvation, suggesting a role for DJ-1 in RNA dynamics...
April 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29675573/triclosan-evoked-neurotoxicity-involves-nmdar-subunits-with-the-specific-role-of-glun2a-in-caspase-3-dependent-apoptosis
#5
Konrad A Szychowski, Agnieszka Wnuk, Joanna Rzemieniec, Małgorzata Kajta, Teresa Leszczyńska, Anna K Wójtowicz
Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitising products. A number of studies have shown the presence of TCS in different human tissues such as blood, adipose tissue, the liver, brain as well as in breast milk and urine. N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are widely expressed in the central nervous system and which play key roles in excitatory synaptic transmission. There is, however, no data on the involvement of NMDAR subunits in the apoptotic and neurotoxic effects of TCS...
April 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29674592/synaptic-transmission-from-subplate-neurons-controls-radial-migration-of-neocortical-neurons
#6
Chiaki Ohtaka-Maruyama, Mayumi Okamoto, Kentaro Endo, Minori Oshima, Noe Kaneko, Kei Yura, Haruo Okado, Takaki Miyata, Nobuaki Maeda
The neocortex exhibits a six-layered structure that is formed by radial migration of excitatory neurons, for which the multipolar-to-bipolar transition of immature migrating multipolar neurons is required. Here, we report that subplate neurons, one of the first neuron types born in the neocortex, manage the multipolar-to-bipolar transition of migrating neurons. By histochemical, imaging, and microarray analyses on the mouse embryonic cortex, we found that subplate neurons extend neurites toward the ventricular side of the subplate and form transient glutamatergic synapses on the multipolar neurons just below the subplate...
April 20, 2018: Science
https://www.readbyqxmd.com/read/29672107/combined-administration-of-mk-801-and-cycloheximide-produces-a-delayed-potentiation-of-fear-discrimination-memory-extinction
#7
Daniel E Kochli, Tiffany L Campbell, Ethan W Hollingsworth, Rain S Lab, Abagail F Postle, Megan M Perry, Victoria M Mordzinski, Jennifer J Quinn
Mixed evidence exists regarding the role of N-methyl-D-aspartate (NMDA) receptors in memory reconsolidation. We provide no evidence that NMDA receptors are involved with memory reconsolidation, but instead demonstrate that prereactivation systemic MK-801 injection, combined with postreactivation intrabasolateral amygdala (BLA) cycloheximide infusion, produces a delayed potentiation of extinction learning. These data suggest that an interaction between NMDA antagonism and protein synthesis inhibition may enhance extinction by exerting effects outside of the intended reconsolidation manipulation window...
April 2018: Behavioral Neuroscience
https://www.readbyqxmd.com/read/29671419/trpm2-a-candidate-therapeutic-target-for-treating-neurological-diseases
#8
REVIEW
Jillian Corinne Belrose, Michael Frederick Jackson
Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+ )-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2 activation provokes aberrant intracellular Ca2+ accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. In addition to research identifying a role for TRPM2 in disease, progress has been made in the identification of physiological functions of TRPM2 in the brain, including recent evidence that TRPM2 is necessary for the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticity at glutamate synapses...
April 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29671352/huntington-s-disease-novel-therapeutic-perspectives-hanging-in-the-balance
#9
Ana Saavedra, Gerardo García-Díaz Barriga, Esther Pérez-Navarro, Jordi Alberch
Huntington's disease (HD), an autosomal dominant neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin gene, has long been characterized by the presence of motor symptoms due to the loss of striatal projection neurons. Cognitive dysfunction and neuropsychiatric symptoms are also present and they occur in the absence of cell death in most mouse models, pointing to neuronal dysfunction and abnormal synaptic plasticity as causative mechanisms. Areas covered: Here, we focus on those common mechanisms altered by the presence of mutant huntingtin affecting corticostriatal and hippocampal function as therapeutic targets that could prove beneficial to ameliorate both cognitive and motor function in HD...
April 19, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29670547/medications-used-for-cognitive-enhancement-in-patients-with-schizophrenia-bipolar-disorder-alzheimer-s-disease-and-parkinson-s-disease
#10
REVIEW
Wen-Yu Hsu, Hsien-Yuan Lane, Chieh-Hsin Lin
Background/aims: Cognitive impairment, which frequently occurs in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease, has a significant impact on the daily lives of both patients and their family. Furthermore, since the medications used for cognitive enhancement have limited efficacy, the issue of cognitive enhancement still remains a clinically unsolved challenge. Sampling and methods: We reviewed the clinical studies (published between 2007 and 2017) that focused on the efficacy of medications used for enhancing cognition in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29670280/mechanism-of-nmda-receptor-channel-block-by-mk-801-and-memantine
#11
Xianqiang Song, Morten Ø Jensen, Vishwanath Jogini, Richard A Stein, Chia-Hsueh Lee, Hassane S Mchaourab, David E Shaw, Eric Gouaux
The NMDA (N-methyl-D-aspartate) receptor transduces the binding of glutamate and glycine, coupling it to the opening of a calcium-permeable ion channel 1 . Owing to the lack of high-resolution structural studies of the NMDA receptor, the mechanism by which ion-channel blockers occlude ion permeation is not well understood. Here we show that removal of the amino-terminal domains from the GluN1-GluN2B NMDA receptor yields a functional receptor and crystals with good diffraction properties, allowing us to map the binding site of the NMDA receptor blocker, MK-801...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29669266/the-strength-of-reward-related-learning-depends-on-the-degree-of-activation-of-ventral-tegmental-area-dopamine-neurons
#12
E Galaj, R Ranaldi
We tested whether (1) the capacity of a reward-associated conditioned stimulus (CS) to cause conditioned activation of ventral tegmental area (VTA) dopamine (DA) neurons is associated with its capacity to elicit conditioned approach responses and (2) whether the acquisition of these capacities by a CS requires N-methyl-D-aspartate (NMDA) and muscarinic acetylcholine (mACh) receptor stimulation. Rats were trained to emit a conditioned approach response to a light CS that was previously paired with food and were treated systemically with scopolamine (a mACh receptor antagonist) or MK-801 a (NMDA receptor antagonist) either prior to each conditioning session (during which animals experienced paired CS and food presentations) or prior to the conditioned approach (CS-only)...
April 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29668918/glutamatergic-signaling-drives-ketamine-mediated-response-in-depression-evidence-from-dynamic-causal-modeling
#13
Jessica R Gilbert, Julia S Yarrington, Kathleen E Wills, Allison C Nugent, Carlos A Zarate
Background: The glutamatergic modulator ketamine has rapid antidepressant effects in individuals with major depressive disorder (MDD) and bipolar depression. Thus, modulating glutamatergic transmission may be critical to effectively treating depression, though the mechanisms by which this occurs are not fully understood. Methods: This double-blind, crossover, placebo-controlled study analyzed data from 18 drug-free MDD subjects and 18 heathy controls who received a single intravenous infusion of ketamine hydrochloride (0...
April 13, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29665767/nano-cuo-impairs-spatial-cognition-associated-with-inhibiting-hippocampal-ltp-via-affecting-glutamatergic-neurotransmission-in-rats
#14
Xiaoliang Li, Wei Sun, Lei An
Manufactured metal nanoparticles and their applications are continuously expanding because of their unique characteristics while their increasing use may predispose to potential health problems. Several studies have reported the adverse effects of copper oxide nanoparticles (nano-CuO) relative to ecotoxicity and cell toxicity, whereas little is known about the neurotoxicity of nano-CuO. The present study aimed to examine its effects on spatial cognition, hippocampal function, and the possible mechanisms. Male Wistar rats were used to establish an animal model, and nano-CuO was administered at a dose of 0...
January 1, 2018: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/29661378/differential-role-of-nitric-oxide-in-the-psychedelic-symptoms-induced-by-racemic-ketamine-and-esketamine-in-human-volunteers
#15
K Jonkman, R van der Schrier, M van Velzen, L Aarts, E Olofsen, E Sarton, M Niesters, A Dahan
BACKGROUND: Animal studies suggest that N-methyl-d-aspartate receptor (NMDAR) hypofunction and subsequent decline in intracellular nitric oxide (NO) are responsible for development of ketamine-induced psychedelic symptoms. To examine this mechanism in humans, we administered the NO donor sodium nitroprusside during infusion of racemic ketamine (RS-ketamine), containing equal amounts of S(+)- and R(-)-ketamine isomers, or esketamine, containing just the S(+)-isomer. METHODS: In this randomised, double blind, placebo-controlled crossover study, healthy volunteers were treated with sodium nitroprusside 0...
May 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29658368/the-aaa-atpase-thorase-is-neuroprotective-against-ischemic-injury
#16
Jianmin Zhang, Jia Yang, Huaishan Wang, Omar Sherbini, Matthew J Keuss, George Ke Umanah, Emily Ling-Lin Pai, Zhikai Chi, Kaisa Ma Paldanius, Wei He, Hong Wang, Shaida A Andrabi, Ted M Dawson, Valina L Dawson
Neuronal preconditioning in vitro or in vivo with a stressful but non-lethal stimulus leads to new protein expression that mediates a profound neuroprotection against glutamate excitotoxicity and experimental stroke. The proteins that mediate neuroprotection are relatively unknown and under discovery. Here we find that the expression of the AAA + ATPase Thorase is induced by preconditioning stimulation both in vitro and in vivo. Thorase provides neuroprotection in an ATP-dependent manner against oxygen-glucose deprivation (OGD) neurotoxicity or glutamate N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in vitro...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29656951/auditory-system-target-engagement-during-plasticity-based-interventions-in-schizophrenia-a-focus-on-modulation-of-n-methyl-d-aspartate-type-glutamate-receptor-function
#17
REVIEW
Joshua T Kantrowitz, Neal R Swerdlow, Walter Dunn, Sophia Vinogradov
Cognitive deficits are predictive of long-term social and occupational functional deficits in schizophrenia but are currently without gold-standard treatments. In particular, augmentation of auditory cortical neuroplasticity may represent a rate-limiting first step before addressing higher-order cognitive deficits. We review the rationale for N-methyl-d-aspartate-type glutamate receptor (NMDAR) modulators as treatments for auditory plasticity deficits in schizophrenia, along with potential serum and electroencephalographic target engagement biomarkers for NMDAR function...
February 22, 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
https://www.readbyqxmd.com/read/29656875/structural-mechanism-of-functional-modulation-by-gene-splicing-in-nmda-receptors
#18
Michael C Regan, Timothy Grant, Miranda J McDaniel, Erkan Karakas, Jing Zhang, Stephen F Traynelis, Nikolaus Grigorieff, Hiro Furukawa
Alternative gene splicing gives rise to N-methyl-D-aspartate (NMDA) receptor ion channels with defined functional properties and unique contributions to calcium signaling in a given chemical environment in the mammalian brain. Splice variants possessing the exon-5-encoded motif at the amino-terminal domain (ATD) of the GluN1 subunit are known to display robustly altered deactivation rates and pH sensitivity, but the underlying mechanism for this functional modification is largely unknown. Here, we show through cryoelectron microscopy (cryo-EM) that the presence of the exon 5 motif in GluN1 alters the local architecture of heterotetrameric GluN1-GluN2 NMDA receptors and creates contacts with the ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, which are absent in NMDA receptors lacking the exon 5 motif...
April 10, 2018: Neuron
https://www.readbyqxmd.com/read/29651654/in-the-telencephalon-glun2c-nmda-receptor-subunit-mrna-is-predominately-expressed-in-glial-cells-and-glun2d-mrna-in-interneurons
#19
Hassan A Alsaad, Nicholas W DeKorver, Zhihao Mao, Shashank M Dravid, Jyothi Arikkath, Daniel T Monaghan
N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the brain with high concentrations in the telencephalon where they modulate synaptic plasticity, working memory, and other functions. While the actions of the predominate GluN2 NMDAR subunits, GluN2A and GluN2B are relatively well understood, the function of GluN2C and GluN2D subunits in the telencephalon is largely unknown. To better understand the possible role of GluN2C subunits, we used fluorescence in situ hybridization (FISH) together with multiple cell markers to define the distribution and type of cells expressing GluN2C mRNA...
April 12, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29651625/clinical-characteristics-and-prognosis-of-severe-anti-n-methyl-d-aspartate-receptor-encephalitis-patients
#20
Yan Zhang, Gang Liu, Mengdi Jiang, Weibi Chen, Yanbo He, Yingying Su
BACKGROUND AND PURPOSE: Data concerning the characteristics and duration of the critical manifestations, treatment response, and long-term outcomes of severe anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients compared to those of non-severe patients are limited. This observational study was performed to explore the clinical characteristics and long-term outcomes of severe anti-NMDAR encephalitis patients. METHODS: According to their characteristics on admission to the neurology intensive care unit, patients with anti-NMDAR encephalitis were divided into a severe group and a non-severe group...
April 12, 2018: Neurocritical Care
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