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N-methyl-D-aspartate

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https://www.readbyqxmd.com/read/29043770/a-novel-negative-allosteric-modulator-selective-for-glun2c-2d-containing-nmda-receptors-inhibits-synaptic-transmission-in-hippocampal-interneurons
#1
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...
October 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29042205/postnatal-administration-of-memantine-rescues-tnf-%C3%AE-induced-decreased-hippocampal-precursor-proliferation
#2
Zhongke Wang, Xie He, Xiaotang Fan
Pro-inflammatory cytokine exposure in early postnatal life triggers clear neurotoxic effects on the developing hippocampus. Tumor necrosis factor alpha (TNF-α) is one of the inflammatory mediators and is a potent inhibitor of neurogenesis. Memantine (MEM) is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that has been demonstrated to increase the proliferation of hippocampal progenitor cells. However, the effects of MEM on TNF-α-mediated impairment of hippocampal precursor proliferation remain unclear...
October 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29040795/case-presentation-of-anti-nmda-receptor-encephalitis-in-a-4-year-old-boy
#3
Daniel A Gbadero, Emmanuel O Adegbite, Jean-Baptist LePichon, Tina M Slusher
We report a case of a 4-year-old boy from Oyo, Nigeria, presenting with prolonged seizures and coma with the subsequent development of oro-lingual-facial dyskinesia with frequent tongue thrusting, dysconjugate gaze and choreoathetoid movements of the limbs because of autoimmune encephalitis consistent with anti-N-methyl-D-aspartate (anti-NMDAR) encephalitis.
October 6, 2017: Journal of Tropical Pediatrics
https://www.readbyqxmd.com/read/29038420/effects-of-different-training-loads-on-emotional-state-and-mrna-and-protein-expressions-of-n-methyl-d-aspartate-receptor-subunits-postsynaptic-density-95-and-kinesin-family-member-17-in-hippocampus-of-rats
#4
Hefei Ren, Xinyi Yu, Liren Yu, Yinguo Zhang, Hong Xie, Na Shi, Lijun Chen
BACKGROUND Emotional state can be affected by different training loads. The aim of this study was to explore the changes of rat emotional state, as well as the mRNA and protein expressions of N-methyl-D-aspartate receptors (NMDARs), postsynaptic density 95 (PSD-95), and kinesin family member 17 (KIF-17) in the hippocampus, by long-term moderate-intensity and high-intensity training models in rats. MATERIAL AND METHODS The exercise model of SD rats was set up by treadmill running of moderate and high intensities for 4 weeks...
October 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29038006/role-of-ca1-gabaa-and-gabab-receptors-on-learning-deficit-induced-by-d-ap5-in-passive-avoidance-step-through-task
#5
Mohaddeseh Ebrahimi-Ghiri, Masoumeh Rostampour, Mehdi Jamshidi-Mehr, Mohammad Nasehi, Mohammad-Reza Zarrindast
To investigate the interaction between hippocampal γ-aminobutyric acid GABAA receptor (GABAAR) or GABAB receptor (GABABR) and N-methyl-D-aspartate receptor (NMDAR) in the acquisition of passive avoidance memory in rats, we used GABAA or GABAB agents, D-AP5 (as a NMDAR antagonist), and a combination of the mentioned drugs in a step-through task. All agents were microinjected into the intra-CA1 regions at a volume of 1 µl/rat, prior to training. GABAAR agonist muscimol (0.2 µg/rat), selective GABABR agonist baclofen (0...
October 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29037878/risperidone-ameliorates-cognitive-deficits-promotes-hippocampal-proliferation-and-enhances-notch-signaling-in-a-murine-model-of-schizophrenia
#6
Fen Xue, Yun-Chun Chen, Cui-Hong Zhou, Ying Wang, Min Cai, Wen-Jun Yan, Rui Wu, Hua-Ning Wang, Zheng-Wu Peng
Antipsychotic agents have been reported to promote hippocampal neurogenesis and improve cognitive deficits; yet, the molecular mechanisms underlying these actions remain unclear. In the present study, we used a murine model of schizophrenia induced by 5-day intraperitoneal injection with the non-competitive N-methyl-d-aspartate receptor antagonist MK801 (0.3mg/kg/day) to assess cognitive behavioral deficits, changes in Notch signaling, and cellular proliferation in the hippocampus of adult male C57BL/6 mice after 2-week administration of risperidone (Rip, 0...
October 13, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29033788/zinc-as-a-neuromodulator-in-the-central-nervous-system-with-a-focus-on-the-olfactory-bulb
#7
REVIEW
Laura J Blakemore, Paul Q Trombley
The olfactory bulb (OB) is central to the sense of smell, as it is the site of the first synaptic relay involved in the processing of odor information. Odor sensations are first transduced by olfactory sensory neurons (OSNs) before being transmitted, by way of the OB, to higher olfactory centers that mediate olfactory discrimination and perception. Zinc is a common trace element, and it is highly concentrated in the synaptic vesicles of subsets of glutamatergic neurons in some brain regions including the hippocampus and OB...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29031411/in%C3%A2-vivo-brain-glycine-and-glutamate-concentrations-in-patients-with-first-episode-psychosis-measured-by-echo-time-averaged-proton-magnetic-resonance-spectroscopy-at-4t
#8
Sang-Young Kim, Marc J Kaufman, Bruce M Cohen, J Eric Jensen, Joseph T Coyle, Fei Du, Dost Öngür
BACKGROUND: Accumulating evidence suggests the involvement of abnormal glutamateric neurotransmission and N-methyl-D-aspartate receptor hypofunction in the pathophysiology of psychotic disorders. The purpose of this study was to quantify in vivo glutamate (Glu) and glycine (Gly) levels in patients with first-episode psychosis as well as age-matched healthy control subjects with magnetic resonance spectroscopy (MRS). METHODS: The subjects were 46 patients with first-episode psychosis (20 with a schizophrenia spectrum disorder, 26 with bipolar disorder) and 50 age-matched healthy control subjects...
September 7, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29030575/adolescent-ethanol-exposure-enhances-nmda-receptor-mediated-currents-in-hippocampal-neurons-reversal-by-gabapentin
#9
H S Swartzwelder, Maeng-Hee Park, Shawn Acheson
Adolescent intermittent ethanol (AIE) exposure compromises neural function into adulthood. We have reported that astrocyte-secreted thrombospondins, and their target neuronal receptors (α2δ-1) are upregulated in the hippocampus in adulthood after AIE, suggesting aberrant excitatory synaptogenesis and hyperexcitability in memory-related circuits. Gabapentin antagonizes the interaction of thrombospondins (TSPs) with the α2δ-1 receptor, and thus may reverse or ameliorate the effects of AIE on hippocampal function...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030082/adx-47273-a-mglu5-receptor-positive-allosteric-modulator-attenuates-deficits-in-cognitive-flexibility-induced-by-withdrawal-from-binge-like-ethanol-exposure-in-rats
#10
Marta Marszalek-Grabska, Ewa Gibula-Bruzda, Anna Bodzon-Kulakowska, Piotr Suder, Kinga Gawel, Sylwia Talarek, Joanna Listos, Ewa Kedzierska, Wojciech Danysz, Jolanta H Kotlinska
Repeated exposure to and withdrawal from ethanol induces deficits in spatial reversal learning. Data indicate that metabotropic glutamate 5 (mGlu5) receptors are implicated in synaptic plasticity and learning and memory. These receptors functionally interact with N-methyl-d-aspartate (NMDA) receptors, and activation of one type results in the activation of the other. We examined whether (S)-(4-fluorophenyl)(3-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl (ADX-47273), a positive allosteric modulator (PAM) of mGlu5 receptor, attenuates deficits in reversal learning induced by withdrawal (11-13days) from 'binge-like' ethanol input (5...
October 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29029785/a-single-dose-of-cocaine-potentiates-glutamatergic-synaptic-transmission-onto-locus-coeruleus-neurons
#11
Feipeng Zhu, Qihui Wu, Jie Li, Katarzyna Grycel, Bing Liu, Xiaoxuan Sun, Li Zhou, Ruiyin Jiao, Rui Song, Younus M Khan, Qinglong Wang, Lun Wang, Yongxin Xu, Jin Li, Bo Zhang, Zhuan Zhou
The brainstem locus coeruleus (LC), the primary norepinephrinergic (NE) nucleus in the brain, has been implicated in the abuse of drugs such as opioids. However, whether and how the LC-NE system is involved in cocaine addiction remains elusive. Here, we demonstrated cocaine-evoked synaptic plasticity of glutamatergic transmission onto LC neurons as one of the earliest traces occurring after a single injection of cocaine. Twenty-four hours after mice were injected intraperitoneally with cocaine, the evoked α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated synaptic transmission onto LC neurons were strongly potentiated without major effect on N-methyl-d-aspartate receptor (NMDAR) mediated synaptic transmission...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29029433/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#12
Zhiwen Zeng, Dejun Wang, Uma Gaur, Liao Rifang, Haitao Wang, Wenhua Zheng
Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these effects of IGF-1 were abolished by H2O2 at 200μM concentration which did not cause any significant toxicity to cells itself in our experiments...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029408/rnai-targeting-nogo-receptor-enhanced-survival-and-proliferation-of-murine-retinal-ganglion-cells-during-n-methyl-d-aspartate-induced-optic-nerve-crush
#13
Kun Zeng, Bo Zhong, Xiao-Li Shen, Min Fang, Bao-Tao Lin, Da-Hui Ma
We investigated the effects of lentivirus-mediated RNAi targeting of Nogo Receptor (NgR) on the proliferation and survival of murine retinal ganglion cells (mRGCs) in vitro and in vivo. Cultured mRGCs and C57BL/6 male mice were divided into 4 experimental groups: blank, model [100 μM N-methyl-D-aspartate (NMDA)], nscRNA (100 μM NMDA+ nscRNA vectors) and siNgR (100 μM NMDA+ siNgR vectors). CCK-8 and flow cytometry analyses revealed that silencing NgR enhanced proliferation, cell cycling and survival of NMDA-treated mRGCs...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029302/acute-kynurenine-challenge-disrupts-sleep-wake-architecture-and-impairs-contextual-memory-in-adult-rats
#14
Ana Pocivavsek, Annalisa M Baratta, Jessica A Mong, Shaun S Viechweg
Study Objectives: Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction. Modest increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts as an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors in the brain, result in cognitive impairments. As glutamatergic and cholinergic neurotransmissions are critically involved in modulation of sleep, our current experiments tested the hypothesis that elevated KYNA adversely impacts sleep quality...
September 28, 2017: Sleep
https://www.readbyqxmd.com/read/29027122/hi1a-as-a-novel-neuroprotective-agent-for-ischemic-stroke-by-inhibition-of-acid-sensing-ion-channel-1a
#15
Yandong Ren, Chengchong Li, Jinlong Chang, Rui Wang, Yuhua Wang, Xiang-Ping Chu
Strokes are the second-leading cause of death worldwide, and the cellular and molecular mechanisms underlying stroke-induced brain damage are still uncertain. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA). However, rtPA has a narrow therapeutic timeframe of 3-4.5 h, and only approximately 5% of stroke patients can benefit from rtPA treatment. Neuroprotective agents, such as N-methyl-D-aspartate receptor antagonists, have shown great promise in preclinical studies...
October 13, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29026836/anti-n-methyl-d-aspartate-receptor-encephalitis-that-aggravates-after-acinetobacter-baumannii-pneumonia-a-case-report
#16
Cheng C Wang, Da J Li, Yi Q Xia, Kai Liu
We report an atypical case of anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE). A 27-year-old man diagnosed with ANMDARE received immunotherapy and had a good recovery. However, within one month, he developed severe status epilepticus and decreased level of conscience with new hyperpyrexia and dyspnea, and was admitted to the emergency intensive care unit. Acinetobacter baumanii were found in the sputum culture; and anti-NMDAR antibodies were positive (titer: 1/80) in the cerebrospinal fluid. Repeated immunotherapy was administered with antibacterial agents, and the patient recovered except for mild psychiatric sequelae...
September 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/29025687/serine-racemase-and-d-serine-in-the-amygdala-are-dynamically-involved-in-fear-learning
#17
Darrick T Balu, Kendall Taylor Presti, Cathy C Y Huang, Kevin Muszynski, Inna Radzishevsky, Herman Wolosker, Guia Guffanti, Kerry J Ressler, Joseph T Coyle
BACKGROUND: The amygdala is a central component of the neural circuitry that underlies fear learning. N-methyl-D-aspartate receptor-dependent plasticity in the amygdala is required for pavlovian fear conditioning and extinction. N-methyl-D-aspartate receptor activation requires the binding of a coagonist, D-serine, which is synthesized from L-serine by the neuronal enzyme serine racemase (SR). However, little is known about SR and D-serine function in the amygdala. METHODS: We used immunohistochemical methods to characterize the cellular localization of SR and D-serine in the mouse and human amygdala...
August 26, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29023630/the-hmgb1-is-increased-in-csf-of-patients-with-an-anti-nmdar-encephalitis
#18
P Ai, X Zhang, Z Xie, G Liu, X Liu, S Pan, H Wang
BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Interleukin (IL)-6 and IL-17A may play important roles in the pathogenesis of this disease. High-mobility group box protein 1 (HMGB1), a small but highly conserved ubiquitous protein, is recognized to be a potent innate inflammatory mediator that can activate the nuclear factor light chain enhancer of activated B cells and release cytokines such as IL-6 and IL-17A when released extracellularly...
October 12, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/29022871/a-postmortem-analysis-of-nmda-ionotropic-and-group-1-metabotropic-glutamate-receptors-in-the-nucleus-accumbens-in-schizophrenia
#19
Jeremy S Lum, Samuel J Millard, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
BACKGROUND: The nucleus accumbens (NAcc) has been implicated in the pathology and treatment of schizophrenia. Recent postmortem evidence suggests a hyperglutamatergic state in the NAcc. With the present study we aimed to explore possible glutamatergic alterations in the NAcc of a large schizophrenia cohort. METHODS: We performed immunoblots on postmortem NAcc samples from 30 individuals who had schizophrenia and 30 matched controls. We examined the protein expression of primary glutamatergic receptors, including the N-methyl-D-aspartate (NMDA) receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate receptor (mGluR1 and mGluR5; dimeric and monomeric forms)...
October 6, 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29019687/simulated-dynamics-of-glycans-on-ligand-binding-domain-of-nmda-receptors-reveals-strong-dynamic-coupling-between-glycans-and-protein-core
#20
Anton V Sinitskiy, Vijay S Pande
N-methyl-D-aspartate (NMDA) receptors, key neuronal receptors playing the central role in learning and memory, are heavily glycosylated in vivo. Astonishingly little is known about the structure, dynamics and physiological relevance of glycans attached to them. We recently demonstrated that certain glycans on the ligand binding domain (LBD) of NMDA receptors (NMDARs) can serve as intramolecular potentiators, changing EC50 of NMDAR co-agonists. In this work, we use molecular dynamics trajectories, in aggregate 86...
October 11, 2017: Journal of Chemical Theory and Computation
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