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https://www.readbyqxmd.com/read/29793153/effects-of-mg-2-on-recovery-of-nmda-receptors-from-inhibition-by-memantine-and-ketamine-reveal-properties-of-a-second-site
#1
Nathan G Glasgow, Madeleine R Wilcox, Jon W Johnson
Memantine and ketamine are NMDA receptor (NMDAR) open channel blockers that are thought to act via similar mechanisms at NMDARs, but exhibit divergent clinical effects. Both drugs act by entering open NMDARs and binding at a site deep within the ion channel (the deep site) at which the endogenous NMDAR channel blocker Mg2+ also binds. Under physiological conditions, Mg2+ increases the IC50 s of memantine and ketamine through competition for binding at the deep site. Memantine also can inhibit NMDARs after associating with a second site accessible in the absence of agonist, a process termed second site inhibition (SSI) that is not observed with ketamine...
May 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29792596/a-swiss-army-knife-for-targeting-receptors
#2
Johansen B Amin, Lonnie P Wollmuth
A compound can change the activity of NMDA receptors in some regions of a synapse without affecting those in other regions.
May 24, 2018: ELife
https://www.readbyqxmd.com/read/29792150/synthesis-and-biological-evaluation-of-novel-2-3-disubstituted-benzofuran-analogues-of-gaba-as-neurotropic-agents
#3
Arturo Coaviche-Yoval, Hector Luna, Ricardo Tovar-Miranda, Marvin Antonio Soriano-Ursua, Jose G Trujillo-Ferrara
BACKGROUND: Benzofurans are heterocyclic compounds with neurotropic activity. Some have been developed for the treatment of acute and degenerative neuronal injuries. OBJECTIVE: To evaluate the in silico binding of some promising benzofurans on the GABA receptors, and the in vivo neurotropic activity of benzofuran analogues (BZF 6-10) of gamma-aminobutyric acid (GABA) on a seizure model. METHODS: The ligands with the best physicochemical attributes were docked on two GABA receptors (the alpha-1 subunit of GABAA-R and GBR1 subunit of GABAB-R)...
May 23, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29790100/the-neurogenesis-actuator-and-nr2b-nmda-receptor-antagonist-ro25-6981-consistently-improves-spatial-memory-retraining-via-brain-region-specific-gene-expression
#4
Marina A Gruden, Alexander M Ratmirov, Zinaida I Storozheva, Olga A Solovieva, Vladimir V Sherstnev, Robert D E Sewell
NR2B-containing NMDA (NR2B/NMDA) receptors are important in controlling neurogenesis and are involved in generating spatial memory. Ro25-6981 is a selective antagonist at these receptors and actuates neurogenesis and spatial memory. Inter-structural neuroanatomical profiles of gene expression regulating adult neurogenesis and neuroapoptosis require examination in the context of memory retrieval and reversal learning. The aim was to investigate spatial memory retrieval and reversal learning in relation to gene expression-linked neurogenetic processes following blockade of NR2B/NMDA receptors by Ro25-6981...
May 22, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29790025/ampar-mediated-interictal-discharges-in-neurons-of-entorhinal-cortex-experiment-and-model
#5
A V Chizhov, D V Amakhin, A V Zaizev, L G Magazanik
The mechanisms of interictal discharges (IID) were studied under the conditions of the 4-aminopyridine model of spontaneous epileptiform activity in surviving rat brain slice preparations. Addition of the agents blocking GABA and NMDA receptors failed to inhibit IID generation in the entorhinal cortex. A mathematical model of IID has been developed on the basis of the excitatory neuron interaction mediated by the AMPA receptor. Short-term synaptic depression and slow afterspike-hyperpolarization are the key factors required to terminate a single IID...
March 2018: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/29789380/metaplasticity-in-the-visual-cortex-crosstalk-between-visual-experience-and-reactive-oxygen-species
#6
José Francis-Oliveira, Guilherme Shuigueto Vilar Higa, Lívia Mendonça Munhoz Dati, Ianê Carvalho Shieh, Roberto De Pasquale
Metaplasticity is the regulation of synaptic plasticity based on the history of previous synaptic activation. This concept was formulated after observing that synaptic changes in the visual cortex are not fixed, but dynamic, and dependent on the history of visual information flux. In visual cortical neurons, sustained synaptic stimulation activate the enzymatic complex NOX2, resulting in the generation of reactive oxygen species (ROS). NOX2 is the main molecular structure responsible for translating neural activity into redox modulation of intracellular signaling pathways involved in plastic changes...
May 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29788757/expression-of-nmda-receptor-subunits-in-human-blood-lymphocytes-a-peripheral-biomarker-in-online-computer-game-addiction
#7
Mitra-Sadat Sadat-Shirazi, Nasim Vousooghi, Bentolhoda Alizadeh, Seyed Mohammad Makki, Seyed Zeinolabedin Zarei, Shahrzad Nazari, Mohammad Reza Zarrindast
Background and aims Repeated performance of some behaviors such as playing computer games could result in addiction. The NMDA receptor is critically involved in the development of behavioral and drug addictions. It has been claimed that the expression level of neurotransmitter receptors in the brain may be reflected in peripheral blood lymphocytes (PBLs). Methods Here, using a real-time PCR method, we have investigated the mRNA expression of GluN2A, GluN2D, GluN3A, and GluN3B subunits of the NMDA receptor in PBLs of male online computer game addicts (n = 25) in comparison with normal subjects (n = 26)...
May 23, 2018: Journal of Behavioral Addictions
https://www.readbyqxmd.com/read/29787770/lateral-hypothalamic-orexin-glucose-inhibited-neurons-may-regulate-reward-based-feeding-by-modulating-glutamate-transmission-in-the-ventral-tegmental-area
#8
Suraj B Teegala, Zhenyu Sheng, Miloni S Dalal, Pamela R Hirschberg, Kevin D Beck, Vanessa H Routh
Glucose inhibits ∼60% of lateral hypothalamic (LH) orexin neurons. Fasting increases the activation of LH orexin glucose-inhibited (GI) neurons in low glucose. Increases in spontaneous glutamate excitatory postsynaptic currents (sEPSCs) onto putative VTA DA neurons in low glucose are orexin dependent (Sheng et al., 2014). VTA DA neurons modulate reward-based feeding (Aston-Jones et al., 2010). We tested the hypothesis that increased activation of LH orexin-GI neurons in low glucose increases glutamate signaling onto VTA DA neurons and contributes to reward-based feeding in food restricted animals...
May 19, 2018: Brain Research
https://www.readbyqxmd.com/read/29785583/the-effect-of-delayed-anti-nmdar-encephalitis-recognition-on-disease-outcome
#9
Vlatko Sulentic, Zeljka Petelin Gadze, Filip Derke, Marija Santini, Danira Bazadona, Sibila Nankovic
Anti-NMDA receptor encephalitis is an acute form of brain inflammation that is potentially lethal but has a high probability for recovery with treatment. Although the clinical picture of anti-NMDAR encephalitis is usually recognizable due to its relatively well-known symptoms, the disorder can sometimes present itself in an unpredictable and atypical way. In this case report, we wish to present the influence of different delay times prior to the establishment of diagnosis. Thus, our first patient was diagnosed with anti-NMDAR encephalitis 4 years after the initial symptoms, the second one after 8 years, and the third one after 13 months...
May 21, 2018: Journal of Neurovirology
https://www.readbyqxmd.com/read/29784826/deletion-of-lrrtm1-and-lrrtm2-in-adult-mice-impairs-basal-ampa-receptor-transmission-and-ltp-in-hippocampal-ca1-pyramidal-neurons
#10
Mehdi Bhouri, Wade Morishita, Paul Temkin, Debanjan Goswami, Hiroshi Kawabe, Nils Brose, Thomas C Südhof, Ann Marie Craig, Tabrez J Siddiqui, Robert Malenka
Leucine-rich repeat transmembrane (LRRTM) proteins are synaptic cell adhesion molecules that influence synapse formation and function. They are genetically associated with neuropsychiatric disorders, and via their synaptic actions likely regulate the establishment and function of neural circuits in the mammalian brain. Here, we take advantage of the generation of a LRRTM1 and LRRTM2 double conditional knockout mouse ( LRRTM1,2 cKO) to examine the role of LRRTM1,2 at mature excitatory synapses in hippocampal CA1 pyramidal neurons...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29779156/adolescent-isolation-rearing-produces-a-prepulse-inhibition-deficit-correlated-with-expression-of-the-nmda-glun1-subunit-in-the-nucleus-accumbens
#11
Megan L Fitzgerald, Virginia M Pickel
Adolescence is a transition period during which social interaction is necessary for normal brain and behavior development. Severely abnormal social interactions during adolescence can increase the incidence of lifelong psychiatric disease. Decreased prepulse inhibition (PPI) is a quantifiable hallmark of some psychiatric illnesses in humans and can be elicited in rodents by isolation rearing throughout the adolescent transition period. PPI is a measure of sensorimotor gating in which the nucleus accumbens (Acb) is crucially involved...
May 19, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29778762/object-spatial-and-social-recognition-testing-in-a-single-test-paradigm
#12
Bin Lian, Jun Gao, Nan Sui, Tingyong Feng, Ming Li
Animals have the ability to process information about an object or a conspecific's physical features and location, and alter its behavior when such information is updated. In the laboratory, the object, spatial and social recognition are often studied in separate tasks, making them unsuitable to study the potential dissociations and interactions among various types of recognition memories. The present study introduced a single paradigm to detect the object and spatial recognition, and social recognition of a familiar and novel conspecific...
May 17, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29777761/functional-organization-of-postsynaptic-glutamate-receptors
#13
REVIEW
Nicky Scheefhals, Harold D MacGillavry
Glutamate receptors are the most abundant excitatory neurotransmitter receptors in the brain, responsible for mediating the vast majority of excitatory transmission in neuronal networks. The AMPA- and NMDA-type ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the fast synaptic responses, while metabotropic glutamate receptors (mGluRs) are coupled to downstream signaling cascades that act on much slower timescales. These functionally distinct receptor sub-types are co-expressed at individual synapses, allowing for the precise temporal modulation of postsynaptic excitability and plasticity...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29772491/calpain-inhibition-reduces-nmda-receptor-rundown-in-rat-substantia-nigra-dopamine-neurons
#14
Jerry Zhao, Michel Baudry, Susan Jones
Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca2+ -dependent regulatory protein has not been identified. The role of the Ca2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown...
May 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29771431/study-of-molecular-mechanisms-of-learning-and-memory-impairment-in-neonatal-rats-post-intrauterine-distress-via-the-pathway-of-tau-protein-hyperphosphorylation
#15
X-S Wang, H Huang
OBJECTIVE: To explore the reversion of the excitatory amino acid receptor antagonists against the impairment of learning-memory and the hyperphosphorylation of protein Tau induced by fetal intrauterine distress in neonatal rats. MATERIALS AND METHODS: The analysis of variance of factorial design set up two intervention factors, fetal intrauterine distress (two levels: no fetal intrauterine distress and a course of fetal intrauterine distress) and the excitatory amino acid receptor antagonists (three levels: Saline; NMDA receptor antagonist MK-801; astragalosides)...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29768996/a-systematic-review-on-donepezil-based-derivatives-as-potential-cholinesterase-inhibitors-for-alzheimer-s-disease
#16
Jan Korabecny, Katarina Spilovska, Eva Mezeiova, Ondrej Benek, Radomir Juza, Daniel Kaping, Ondrej Soukup
Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine...
May 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29767953/pharmacological-and-electrophysiological-characterization-of-novel-nmda-receptor-antagonists
#17
Rosana Leiva, Matthew B Phillips, Andreea Larisa Turcu, Esther Gratacòs-Batlle, Lara León-García, Francesc X Sureda, David Soto, Jon W Johnson, Santiago Vazquez
This work reports the synthesis, and pharmacological and electrophysiological evaluation of new N-methyl-D-aspartic acid receptor (NMDAR) channel blocking antagonists featuring polycyclic scaffolds. Changes in the chemical structure modulate the potency and voltage dependence of inhibition. Two of the new antagonists display properties comparable to those of memantine, a clinically approved NMDAR antagonist.
May 16, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29766293/nmda-receptor-subunits-change-in-the-prefrontal-cortex-of-pure-opioid-and-multi-drug-abusers-a-post-mortem-study
#18
Hamidreza Daneshparvar, Mitra-Sadat Sadat-Shirazi, Monir Fekri, Solmaz Khalifeh, Ali Ziaie, Nasrin Esfahanizadeh, Nasim Vousooghi, Mohammad-Reza Zarrindast
Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-D-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers...
May 16, 2018: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/29766040/the-midline-axon-crossing-decision-is-regulated-through-an-activity-dependent-mechanism-by-the-nmda-receptor
#19
Jingxia Gao, Tamara J Stevenson, Adam D Douglass, Joshua P Barrios, Joshua L Bonkowsky
Axon guidance in vertebrates is controlled by genetic cascades as well as by intrinsic activity-dependent refinement of connections. Midline axon crossing is one of the best studied pathfinding models and is fundamental to the establishment of bilaterally symmetric nervous systems. However, it is not known whether crossing requires intrinsic activity in axons, and what controls that activity. Further, a mechanism linking neuronal activity and gene expression has not been identified for axon pathfinding. Using embryonic zebrafish, we found that the NMDA receptor (NMDAR) NR1...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29764453/ampa-ergic-regulation-of-amyloid-%C3%AE-levels-in-an-alzheimer-s-disease-mouse-model
#20
Jane C Hettinger, Hyo Lee, Guojun Bu, David M Holtzman, John R Cirrito
BACKGROUND: Extracellular aggregation of the amyloid-β (Aβ) peptide into toxic multimers is a key event in Alzheimer's disease (AD) pathogenesis. Aβ aggregation is concentration-dependent, with higher concentrations of Aβ much more likely to form toxic species. The processes that regulate extracellular levels of Aβ therefore stand to directly affect AD pathology onset. Studies from our lab and others have demonstrated that synaptic activity is a critical regulator of Aβ production through both presynaptic and postsynaptic mechanisms...
May 15, 2018: Molecular Neurodegeneration
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