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https://www.readbyqxmd.com/read/27913408/neurophysiological-mechanisms-of-cortical-plasticity-impairments-in-schizophrenia-and-modulation-by-the-nmda-receptor-agonist-d-serine
#1
Joshua T Kantrowitz, Michael L Epstein, Odeta Beggel, Stephanie Rohrig, Jonathan M Lehrfeld, Nadine Revheim, Nayla P Lehrfeld, Jacob Reep, Emily Parker, Gail Silipo, Merav Ahissar, Daniel C Javitt
Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27911756/activation-of-group-ii-metabotropic-glutamate-receptors-promotes-ltp-induction-at-schaffer-collateral-ca1-pyramidal-cell-synapses-by-priming-nmda-receptors
#2
Nadia Rosenberg, Urs Gerber, Jeanne Ster
: It is well established that selective activation of group I metabotropic glutamate (mGlu) receptors induces LTD of synaptic transmission at Schaffer collateral-CA1 synapses. In contrast, application of 1S,3R-ACPD, a mixed agonist at group I and group II mGlu receptors, induces LTP. Using whole-cell recordings from CA1 pyramidal cells and field recordings in the hippocampal CA1 region, we investigated the specific contribution of group II mGlu receptors to synaptic plasticity at Schaffer collateral-CA1 synapses in acute slices of adult mice...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903101/d-cycloserine-an-nmda-glutamate-receptor-glycine-site-partial-agonist-induces-acute-increases-in-brain-glutamate-plus-glutamine-and-gaba-comparable-to-ketamine
#3
Joshua T Kantrowitz, Matthew S Milak, Xiangling Mao, Dikoma C Shungu, J John Mann
No abstract text is available yet for this article.
December 1, 2016: American Journal of Psychiatry
https://www.readbyqxmd.com/read/27889096/novel-functional-properties-of-drosophila-cns-glutamate-receptors
#4
Yan Li, Poorva Dharkar, Tae-Hee Han, Mihaela Serpe, Chi-Hon Lee, Mark L Mayer
Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists...
December 7, 2016: Neuron
https://www.readbyqxmd.com/read/27880078/serine-racemase-is-expressed-in-islets-and-contributes-to-the-regulation-of-glucose-homeostasis
#5
Amber D Lockridge, Daniel C Baumann, Brian Akhaphong, Alleah Abrenica, Robert F Miller, Emilyn U Alejandro
NMDA receptors (NMDARs) have recently been discovered as functional regulators of pancreatic β-cell insulin secretion. While these excitatory receptor channels have been extensively studied in the brain for their role in synaptic plasticity and development, little is known about how they work in β-cells. In neuronal cells, NMDAR activation requires the simultaneous binding of glutamate and a rate-limiting co-agonist, such as D-serine. D-serine levels and availability in most of the brain rely on endogenous synthesis by the enzyme serine racemase (Srr)...
November 2016: Islets
https://www.readbyqxmd.com/read/27867000/neuromodulatory-effects-of-the-dorsal-hippocampal-endocannabinoid-system-in-dextromethorphan-morphine-induced-amnesia
#6
Zahra Ghasemzadeh, Ameneh Rezayof
Dextromethorphan which is an active ingredient in many cough medicines has been previously shown to potentiate amnesic effect of morphine in rats. However, the effect of dextromethorphan, that is also a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in combination with morphine on hippocampus-based long term memory has not been well characterized. The aim of the present study was to assess the possible role of endocannabinoid system of the dorsal hippocampus in dextromethorphan /morphine-induced amnesia...
November 17, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27858086/interaction-between-nmda-and-cb2-function-in-the-dorsal-hippocampus-on-memory-consolidation-impairment-an-isobologram-analysis
#7
Mohammad Nasehi, Marziyeh Hajikhani, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast
RATIONALE: Convincing evidence has supported the pivotal role of N-methyl-D-aspartate receptors (NMDARs) and CB2Rs in the regulation of learning and memory. OBJECTIVE: In this study, the role of hippocampal (CA1 region) CB2 receptors on aversive memory consolidation deficit induced by D-AP5, a NMDA receptor antagonist, was evaluated. METHODS: Adult male Wistar rats received cannula implants that bilaterally targeted the CA1 region. Long-term memory was examined using the step-through type of passive avoidance task...
November 17, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27853241/supplementation-with-d-serine-prevents-the-onset-of-cognitive-deficits-in-adult-offspring-after-maternal-immune-activation
#8
Yuko Fujita, Tamaki Ishima, Kenji Hashimoto
Prenatal maternal infection contributes to the etiology of schizophrenia, with D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, playing a role in the pathophysiology of this disease. We examined whether supplementation with D-serine during juvenile and adolescent stages could prevent the onset of cognitive deficits, prodromal and the core symptoms of schizophrenia in adult offspring after maternal immune activation (MIA). Juvenile offspring exposed prenatally to poly(I:C) showed reduced expression of NMDA receptor subunits in the hippocampus...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27847466/glun2a-subunit-containing-nmda-receptors-are-the-preferential-neuronal-targets-of-homocysteine
#9
Dmitry A Sibarov, Polina A Abushik, Rashid Giniatullin, Sergei M Antonov
Homocysteine (HCY) is an endogenous redox active amino acid, best known as contributor to various neurodegenerative disorders. Although it is known that HCY can activate NMDA receptors (NMDARs), the mechanisms of its action on receptors composed of different NMDA receptor subunits remains almost unknown. In this study, using imaging and patch clamp technique in cultured cortical neurons and heterologous expression in HEK293T cells we tested the agonist activity of HCY on NMDARs composed of GluN1 and GluN2A subunits (GluN1/2A receptors) and GluN1 and GluN2B subunits (GluN1/2B receptors)...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27845243/in-vitro-detection-of-oxygen-and-glucose-deprivation-induced-neurodegeneration-and-pharmacological-neuroprotection-based-on-hippocampal-stratum-pyramidale-width
#10
Pınar Öz, Hale Saybaşılı
Ischemia is one of the most prominent risk factors of neurodegenerative diseases such as Alzheimer's disease. The effects of oxygen and glucose depletion in hippocampal tissue due to ischemia can be mimicked in vitro using the oxygen and glucose deprivation (OGD) model. In this study, we applied OGD on acute rat hippocampal slices in order to design an elementary yet quantitative histological technique that compares the neuroprotective effects of (l)-carnitine to known neuroprotectors, such as the N-methyl-d-aspartate (NMDA) receptor antagonist memantine and the gamma-aminobutyric acid (GABA)-B receptor agonist baclofen...
January 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27837332/effects-of-n-methyl-d-aspartate-receptor-ligands-on-sensitivity-to-reinforcer-magnitude-and-delayed-reinforcement-in-a-delay-discounting-procedure
#11
Justin R Yates, Benjamin T Gunkel, Katherine K Rogers, Mallory N Hughes, Nicholas A Prior
RATIONALE: The N-methyl-D-aspartate (NMDA) receptor has been recently identified as an important mediator of impulsive choice, as assessed in delay discounting. Although discounting is independently influenced by sensitivity to reinforcer magnitude and delayed reinforcement, few studies have examined how NMDA receptor ligands differentially affect these parameters. OBJECTIVES: The current study examined the effects of various NMDA receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure...
November 11, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27831563/tissue-type-plasminogen-activator-controls-neuronal-death-by-raising-surface-dynamics-of-extrasynaptic-nmda-receptors
#12
Flavie Lesept, Arnaud Chevilley, Julie Jezequel, Laurent Ladépêche, Richard Macrez, Margaux Aimable, Sophie Lenoir, Thomas Bertrand, Laëtitia Rubrecht, Pascale Galea, Laurent Lebouvier, Karl-Uwe Petersen, Yannick Hommet, Eric Maubert, Carine Ali, Laurent Groc, Denis Vivien
N-methyl-d-aspartate receptors (NMDARs) are ion channels whose synaptic versus extrasynaptic localization critically influences their functions. This distribution of NMDARs is highly dependent on their lateral diffusion at the cell membrane. Each obligatory subunit of NMDARs (GluN1 and GluN2) contains two extracellular clamshell-like domains with an agonist-binding domain and a distal N-terminal domain (NTD). To date, the roles and dynamics of the NTD of the GluN1 subunit in NMDAR allosteric signaling remain poorly understood...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27825808/dissociation-in-the-effects-of-stress-and-d1-receptors-activation-on-basolateral-amygdalar-ltp-in-juvenile-and-adult-animals
#13
Rachel Schayek, Mouna Maroun
Post-weaning or juvenility is a critical developmental stage during which neural structures as the medial prefrontal cortex (mPFC) and amygdala and the neurotransmitter systems undergo major reorganization and thus are susceptible to the effects of environmental factors. Interactions between the mPFC and the amygdala are critical for fear regulation. Changes in plasticity in the projections from the mPFC to the basolateral amygdala (BLA) were previously shown following stress and fear. In the present study, we examined possible differences between adult and PW animals in the (1) effects of exposure to stress on BLA- LTP and (2) the possible dependency of mPFC-BLA LTP on N-methyl-d-aspartate (NMDA) and Dopamine (D) receptors activation...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27815216/pharmacological-evidence-that-a-failure-to-recruit-nmda-receptors-contributes-to-impaired-fear-extinction-retention-in-adolescent-rats
#14
Kathryn D Baker, Rick Richardson
Adolescents, both humans and rodents, exhibit a marked impairment in extinction of fear relative to younger and older groups which could be caused by a failure to efficiently recruit NMDA receptors (NMDARs) in adolescence. It is well-established that systemic administration of NMDAR antagonists (e.g., MK801) before extinction training impairs the retention of extinction in adult and juvenile rodents, but it is unknown whether this is also the case for adolescents. Therefore, in the present study we investigated the effect of pharmacologically manipulating the NMDAR on extinction retention in adolescent rats...
November 1, 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27812957/the-effects-of-verapamil-and-its-combinations-with-glutamate-and-glycine-on-cardiodynamics-coronary-flow-and-oxidative-stress-in-isolated-rat-heart
#15
Isidora Stojic, Ivan Srejovic, Vladimir Zivkovic, Nevena Jeremic, Marko Djuric, Ana Stevanovic, Tamara Milanovic, Dragan Djuric, Vladimir Jakovljevic
The role of N-methyl-D-aspartate receptor (NMDA-R) in heart is still unclear. For these ionotropic glutamate receptors is characteristic the necessity of both co-agonists, glutamate and glycine, for their activation, which primarily allows influx of calcium. The aim of the present study was to examine the effects of verapamil, as a calcium channel blocker, alone and its combination with glycine and/or glutamate on cardiac function, coronary flow, and oxidative stress in isolated rat heart or to examine the effects of potential activation of NMDA-R in isolated rat heart...
November 3, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27807405/glycine-potentiates-ampa-receptor-function-through-metabotropic-activation-of-glun2a-containing-nmda-receptors
#16
Li-Jun Li, Rong Hu, Brendan Lujan, Juan Chen, Jian-Jian Zhang, Yasuko Nakano, Tian-Yuan Cui, Ming-Xia Liao, Jin-Cao Chen, Heng-Ye Man, Hua Feng, Qi Wan
NMDA receptors are Ca(2+)-permeable ion channels. The activation of NMDA receptors requires agonist glutamate and co-agonist glycine. Recent evidence indicates that NMDA receptor also has metabotropic function. Here we report that in cultured mouse hippocampal neurons, glycine increases AMPA receptor-mediated currents independent of the channel activity of NMDA receptors and the activation of glycine receptors. The potentiation of AMPA receptor function by glycine is antagonized by the inhibition of ERK1/2...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27791020/essential-protective-role-of-tumor-necrosis-factor-receptor-2-in-neurodegeneration
#17
Yun Dong, Roman Fischer, Petrus J W Naudé, Olaf Maier, Csaba Nyakas, Maëlle Duffey, Eddy A Van der Zee, Doortje Dekens, Wanda Douwenga, Andreas Herrmann, Eric Guenzi, Roland E Kontermann, Klaus Pfizenmaier, Ulrich L M Eisel
Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed the antithetic effects of the two TNF receptors (TNFR) in the central nervous system, whereby TNFR1 has been associated with inflammatory degeneration and TNFR2 with neuroprotection. We here show the therapeutic potential of selective inhibition of TNFR1 and activation of TNFR2 by ATROSAB, a TNFR1-selective antagonistic antibody, and EHD2-scTNFR2, an agonistic TNFR2-selective TNF, respectively, in a mouse model of NMDA-induced acute neurodegeneration...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27781556/mood-therapeutics-novel-pharmacological-approaches-for-treating-depression
#18
Ioline D Henter, Rafael T de Sousa, Philip W Gold, Andre R Brunoni, Carlos A Zarate, Rodrigo Machado-Vieira
Real-world effectiveness trials suggest that antidepressant efficacy is limited in many patients with mood disorders, underscoring the urgent need for novel therapeutics to treat these disorders. Areas Covered: Here, we review the clinical evidence supporting the use of novel modulators for the treatment of mood disorders, including specific glutamate modulators such as: 1) high-trapping glutamatergic modulators; 2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists; 3) NMDA receptor glycine-site partial agonists; and 4) metabotropic glutamate receptor (mGluR) modulators...
October 26, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27773429/loss-of-glycine-transporter-1-causes-a-subtype-of-glycine-encephalopathy-with-arthrogryposis-and-mildly-elevated-cerebrospinal-fluid-glycine
#19
Alina Kurolap, Anja Armbruster, Tova Hershkovitz, Katharina Hauf, Adi Mory, Tamar Paperna, Ewald Hannappel, Galit Tal, Yusif Nijem, Ella Sella, Muhammad Mahajnah, Anat Ilivitzki, Dov Hershkovitz, Nina Ekhilevitch, Hanna Mandel, Volker Eulenburg, Hagit N Baris
Glycine is a major neurotransmitter that activates inhibitory glycine receptors and is a co-agonist for excitatory glutamatergic N-methyl-D-aspartate (NMDA) receptors. Two transporters, GLYT1 and GLYT2, regulate extracellular glycine concentrations within the CNS. Dysregulation of the extracellular glycine has been associated with hyperekplexia and nonketotic hyperglycinemia. Here, we report four individuals from two families who presented at birth with facial dysmorphism, encephalopathy, arthrogryposis, hypotonia progressing to hypertonicity with startle-like clonus, and respiratory failure...
November 3, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27771572/d-cycloserine-does-not-enhance-the-effects-of-in%C3%A2-vivo-exposure-among-young-people-with-broad-based-anxiety-disorders
#20
Ronald M Rapee, Michael P Jones, Jennifer L Hudson, Gin S Malhi, Heidi J Lyneham, Sophie C Schneider
Use of the partial NMDA receptor agonist d-Cycloserine (DCS) to increase extinction to feared cues among anxious adults has shown mixed, although overall positive effects. Few studies have extended this effect to youth and none have addressed young people with broad-based anxiety such as separation anxiety, social anxiety, or generalised anxiety. In the current trial 51 children and adolescents with diagnosed anxiety disorders, aged 7-14 years received four sessions of graduated, experimenter-led, in vivo exposure to a hierarchy of feared cues relevant to their primary fear...
October 18, 2016: Behaviour Research and Therapy
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