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Glutamate receptors

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https://www.readbyqxmd.com/read/28546056/glutamate-in-dorsolateral-prefrontal-cortex-and-auditory-verbal-hallucinations-in-patients-with-schizophrenia-a-1-h-mrs-study
#1
Branislava Ćurčić-Blake, Leonie Bais, Anita Sibeijn-Kuiper, Marieke Pijnenborg, Henderikus Knegtering, Edith Liemburg, André Aleman
PURPOSE: Glutamatergic models of psychosis propose that dysfunction of N-methyl-d-aspartate (NMDA) receptors, and associated excess of glutamate, may underlie psychotic experiences in people with schizophrenia. However, little is known about the specific relation between glutamate and auditory verbal hallucinations (AVH) in patients with psychosis. In this study, levels of glutamate+glutamine (Glx) in the left lateral prefrontal lobe were determined using proton magnetic resonance spectroscopy ((1)H MRS) to calculate their association with AVH...
May 22, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28545760/identification-of-synaptic-pattern-of-nmda-receptor-subunits-upon-direction-selective-retinal-ganglion-cells-in-developing-and-adult-mouse-retina
#2
Jun-Seok Lee, Hang-Gu Kim, Chang-Jin Jeon
Direction selectivity of the retina is a unique mechanism and critical function of eyes for surviving. Direction-selective retinal ganglion cells (DS RGCs) strongly respond to preferred directional stimuli, but rarely respond to the opposite or null directional stimuli. These DS RGCs are sensitive to glutamate, which is secreted from bipolar cells. Using immunocytochemistry, we studied with the distributions of N-methyl-d-aspartate (NMDA) receptor subunits on the dendrites of DS RGCs in the developing and adult mouse retina...
May 22, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28545724/the-role-of-ca-2-in-cell-death-caused-by-oxidative-glutamate-toxicity-and-ferroptosis
#3
REVIEW
Pamela Maher, Klaus van Leyen, Partha Narayan Dey, Birgit Honrath, Amalia Dolga, Axel Methner
Ca(2+) ions play a fundamental role in cell death mediated by oxidative glutamate toxicity or oxytosis, a form of programmed cell death similar and possibly identical to other forms of cell death like ferroptosis. Ca(2+) influx from the extracellular space occurs late in a cascade characterized by depletion of the intracellular antioxidant glutathione, increases in cytosolic reactive oxygen species and mitochondrial dysfunction. Here, we aim to compare oxidative glutamate toxicity with ferroptosis, address the signaling pathways that culminate in Ca(2+) influx and cell death and discuss the proteins that mediate this...
May 12, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28545490/glutamate-signaling-through-the-nmda-receptor-reduces-the-expression-of-scleraxis-in-plantaris-tendon-derived-cells
#4
Christoph Spang, Ludvig J Backman, Sandrine Le Roux, Jialin Chen, Patrik Danielson
BACKGROUND: A body of evidence demonstrating changes to the glutaminergic system in tendinopathy has recently emerged. This hypothesis was further tested by studying the effects of glutamate on the tenocyte phenotype, and the impact of loading and exposure to glucocorticoids on the glutamate signaling machinery. METHODS: Plantaris tendon tissue and cultured plantaris tendon derived cells were immunohisto-/cytochemically stained for glutamate, N-Methyl-D-Aspartate receptor 1 (NMDAR1) and vesicular glutamate transporter 2 (VGluT2)...
May 25, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28544775/potentiation-of-spinal-glutamatergic-response-in-the-neuron-glia-interactions-underlies-the-intrathecal-il-1%C3%AE-induced-thermal-hyperalgesia-in-rats
#5
Chun-Sung Sung, Zhi-Hong Wen, Chien-Wei Feng, Chun-Hong Chen, Shi-Ying Huang, Nan-Fu Chen, Wu-Fu Chen, Chih-Shung Wong
AIMS: We previously demonstrated that intrathecal IL-1β upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1β-induced nociception in rats. METHODS: The pretreatment effects of MK-801 (5 μg), minocycline (20 μg), and SB203580 (5 μg) on intrathecal IL-1β (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies...
May 19, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28543930/further-analysis-of-acute-antinociceptive-and-anti-inflammatory-actions-of-4-phenylselenyl-7-chloroquinoline-in-mice
#6
Vanessa D G Silva, Angélica S Reis, Mikaela Pinz, Caren A R da Fonseca, Luis Fernando B Duarte, Juliano A Roehrs, Diego Alves, Cristiane Luchese, Ethel A Wilhelm
A new quinoline containing selenium, 4-phenylselenyl-7-chloroquinoline (4-PSQ), was described and synthetized by our research group. Recently, we demonstrated the potential antinociceptive and anti-inflammatory of 4-PSQ. For this reason, the first objective of this study was to expand our previous findings by investigating the contribution of glutamatergic, serotonergic and nitrergic systems to the acute antinociceptive action of this compound. Pretreatment with 4-PSQ (0.01-25 mg/kg, p.o.) reduced the nociception induced by glutamate...
May 23, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28538174/schizophrenia-related-microdeletion-impairs-emotional-memory-through-microrna-dependent-disruption-of-thalamic-inputs-to-the-amygdala
#7
Tae-Yeon Eom, Ildar T Bayazitov, Kara Anderson, Jing Yu, Stanislav S Zakharenko
Individuals with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing psychiatric diseases such as schizophrenia. Individuals with 22q11DS and schizophrenia are impaired in emotional memory, anticipating, recalling, and assigning a correct context to emotions. The neuronal circuits responsible for these emotional memory deficits are unknown. Here, we show that 22q11DS mouse models have disrupted synaptic transmission at thalamic inputs to the lateral amygdala (thalamo-LA projections). This synaptic deficit is caused by haploinsufficiency of the 22q11DS gene Dgcr8, which is involved in microRNA processing, and is mediated by the increased dopamine receptor Drd2 levels in the thalamus and by reduced probability of glutamate release from thalamic inputs...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28536976/memory-and-learning-dysfunction-following-copper-toxicity-biochemical-and-immunohistochemical-basis
#8
Jayantee Kalita, Vijay Kumar, Usha K Misra, Himangsu K Bora
The prototype disease of Cu toxicity in human is Wilson disease, and cognitive impairment is the presenting symptom of it. There is no study correlating Cu-induced excitotoxicity, apoptosis, and astrocytic reaction with memory dysfunction. We report excitotoxicity, apoptosis, and astrocytic reaction of the hippocampus and frontal cortex with memory dysfunction in rat model of Cu toxicity. Thirty-six rats were divided into group I (control) and group II (100 mg/kgBwt/day CuSO4 orally). Y-maze was performed for memory and learning at 0, 30, 60, and 90 days...
May 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28536931/guanosine-promotes-cytotoxicity-via-adenosine-receptors-and-induces-apoptosis-in-temozolomide-treated-a172-glioma-cells
#9
Karen A Oliveira, Tharine A Dal-Cim, Flávia G Lopes, Cláudia B Nedel, Carla Inês Tasca
Gliomas are a malignant tumor group whose patients have survival rates around 12 months. Among the treatments are the alkylating agents as temozolomide (TMZ), although gliomas have shown multiple resistance mechanisms for chemotherapy. Guanosine (GUO) is an endogenous nucleoside involved in extracellular signaling that presents neuroprotective effects and also shows the effect of inducing differentiation in cancer cells. The chemotherapy allied to adjuvant drugs are being suggested as a novel approach in gliomas treatment...
May 23, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28536523/positive-modulatory-interactions-of-nmda-receptor-glun1-2b-ligand-binding-domains-attenuate-antagonists-activity
#10
Douglas Bledsoe, Ceyhun Tamer, Ivana Mesic, Christian Madry, Bradley G Klein, Bodo Laube, Blaise M Costa
N-methyl D-aspartate receptors (NMDAR) play crucial role in normal brain function and pathogenesis of neurodegenerative and psychiatric disorders. Functional tetra-heteromeric NMDAR contains two obligatory GluN1 subunits and two identical or different non-GluN1 subunits that include six different gene products; four GluN2 (A-D) and two GluN3 (A-B) subunits. The heterogeneity of subunit combination facilities the distinct function of NMDARs. All GluN subunits contain an extracellular N-terminal Domain (NTD) and ligand binding domain (LBD), transmembrane domain (TMD) and an intracellular C-terminal domain (CTD)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28535734/investigational-drugs-in-phase-i-and-phase-ii-for-levodopa-induced-dyskinesia
#11
Silvia Cerri, Francesca Siani, Fabio Blandini
prolonged treatment of Parkinson's disease with L-DOPA results in motor complications, including motor fluctuations and involuntary movements known as L-DOPA induced dyskinesias (LIDs). LIDs represent an additional cause of disability for PD patients and a major challenge for the clinical neurologist. Pre-clinical research has provided invaluable insights into the molecular and neural substrates of LIDs, identifying a number of potential targets for new anti-dyskinetic strategies. Areas covered: this review article is centered on drugs currently in Phase I and II clinical trials for LIDs and their relative pharmacological targets, which include glutamate, acetylcholine, serotonin, adrenergic receptors and additional targets of potential therapeutic interest...
May 24, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28535436/microcystin-lr-induces-changes-in-the-gaba-neurotransmitter-system-of-zebrafish
#12
Wei Yan, Li Li, Guangyu Li, Sujuan Zhao
It has been reported that exposure to microcystins altered adult zebrafish swimming performance parameters, but the possible mechanisms of action remain unknown. Neuronal activity depends on the balance between the number of excitatory and inhibitory processes which are associated with neurotransmitters. In the present study, zebrafish embryos (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30μg/L (microcystin-LR) MCLR for 90day until reaching sexual maturity. To investigate the effects of MCLR on the neurotransmitter system, mRNA levels involved in amino acid g-aminobutyric acid (GABA) and glutamate metabolic pathways were tested using quantitative real-time PCR...
May 15, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28534738/optocontrol-of-glutamate-receptor-activity-by-single-side-chain-photoisomerization
#13
Viktoria Klippenstein, Christian Hoppmann, Shixin Ye, Lei Wang, Pierre Paoletti
Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28534263/n-acetylaspartylglutamate-inhibits-heroin-self-administration-and-heroin-seeking-behaviors-induced-by-cue-or-priming-in-rats
#14
Huaqiang Zhu, Miaojun Lai, Weisheng Chen, Disen Mei, Fuqiang Zhang, Huifeng Liu, Wenhua Zhou
Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i...
May 22, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28533177/immunohistochemical-comparison-of-astrocytic-mglur5-upregulation-in-infraorbital-nerve-versus-sciatic-nerve-ligated-rat
#15
Benoit Michot, Ronald Deumens, Emmanuel Hermans
The differential pharmacological responsiveness of cephalic and extra-cephalic neuropathic pain has been proposed to relate to distinct mechanisms that may involve neuroinflammatory reactions mediated by glial cells. Astrocytes are particularly important for neuronal sensitization in neuropathic pain, in part through modulation of glutamatergic transmission. Because the metabotropic glutamate receptor 5 (mGluR5) is involved in the astrocytic regulation of the glutamatergic system, we investigated modifications of its expression in models of cephalic versus extra-cephalic neuropathic pain...
May 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28533163/grin2b-gain-of-function-mutations-are-sensitive-to-radiprodil-a-negative-allosteric-modulator-of-glun2b-containing-nmda-receptors
#16
Brice Mullier, Christian Wolff, Zara Amanda Sands, Philippe Ghisdal, Pierandrea Muglia, Rafal Marian Kaminski, Véronique Marie André
De novo gain of function mutations in GRIN2B encoding the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor have been linked with epileptic encephalopathies, including infantile spasms. We investigated the effects of radiprodil, a selective GluN2B negative allosteric modulator and other non-selective NMDA receptor inhibitors on glutamate currents mediated by NMDA receptors containing mutated GluN2B subunits. The experiments were performed in Xenopus oocytes co-injected with the following human mRNAs: GRIN1/GRIN2B, GRIN1/GRIN2B-R540H, GRIN1/GRIN2B-N615I and GRIN1/GRIN2B-V618G...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28533113/a-novel-serine-racemase-inhibitor-suppresses-neuronal-over-activation-in-vivo
#17
Hisashi Mori, Ryogo Wada, Satoyuki Takahara, Yoshikazu Horino, Hironori Izumi, Tetsuya Ishimoto, Tomoyuki Yoshida, Mineyuki Mizuguchi, Takayuki Obita, Hiroaki Gouda, Shuichi Hirono, Naoki Toyooka
Serine racemase (SRR) is an enzyme that produces d-serine from l-serine. d-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states...
May 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28530802/discovery-of-n-5-fluoropyridin-2-yl-6-methyl-4-pyrimidin-5-yloxy-picolinamide-vu0424238-a-novel-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-subtype-5-selected-for-clinical-evaluation
#18
Andrew S Felts, Alice L Rodriguez, Anna L Blobaum, Ryan D Morrison, Brittney S Bates, Analisa Thompson Gray, Jerri M Rook, Mohammed N Tantawy, Frank W Byers, Sichen Chang, Daryl F Venable, Vincent B Luscombe, Gilles D Tamagnan, Colleen M Niswender, J Scott Daniels, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte
Preclinical evidence in support of the potential utility of mGlu5 NAMs for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. Despite some promising results from clinical studies, no small molecule mGlu5 NAM has yet to reach market. Here we present the discovery and evaluation of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, VU0424238), a compound selected for clinical evaluation. Compound 27 is more than 900-fold selective for mGlu5 versus the other mGlu receptors, and binding studies established a Ki value of 4...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528135/presymptomatically-applied-ampa-receptor-antagonist-prevents-calcium-increase-in-vulnerable-type-of-motor-axon-terminals-of-mice-modeling-amyotrophic-lateral-sclerosis
#19
Roland Patai, Melinda Paizs, Massimo Tortarolo, Caterina Bendotti, Izabella Obál, József I Engelhardt, László Siklós
Increased intracellular calcium (Ca), which might be the consequence of an excess influx through Ca-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, plays a crucial role in degeneration of motor neurons. Previously we demonstrated that the presymptomatic application of AMPA receptor antagonist, talampanel, could reduce Ca elevation in spinal motor neurons of mice carrying the G93A mutation of superoxide dismutase 1 (SOD1), modeling amyotrophic lateral sclerosis (ALS). It remained to be examined whether the remote, functionally semi-autonomous motor axon terminals could be rescued from the Ca overload, or if the terminals, where the degeneration possibly starts, already experience intractable changes at early time points...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527083/shared-mechanisms-of-epilepsy-migraine-and-affective-disorders
#20
Davide Zarcone, Simona Corbetta
Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility...
May 2017: Neurological Sciences
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