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N-methyl-D-aspartate

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https://www.readbyqxmd.com/read/29241198/fam3a-protects-against-glutamate-induced-toxicity-by-preserving-calcium-homeostasis-in-differentiated-pc12-cells
#1
Qing Song, Wen-Li Gou, Yu-Liang Zou
BACKGROUND/AIMS: Stroke is the leading cause of adult disability, and glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key mechanism. FAM3A is the first member of the family with sequence similarity 3 (FAM3) gene family, and its biological function remains largely unknown. We have recently reported that FAM3A exerts protective effects against oxidative stress and mitochondrial dysfunction in HT22 cells. METHODS: Here, we investigated the protective effects of FAM3A using a glutamate-induced neuronal injury model in nerve growth factor (NGF)-differentiated PC12 cells...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29239974/additive-and-subadditive-antiallodynic-interactions-between-%C3%AE-opioid-agonists-and-n-methyl-d-aspartate-antagonists-in-male-rhesus-monkeys
#2
Jeremy C Cornelissen, Floyd F Steele, Kenner C Rice, Katherine L Nicholson, Matthew L Banks
μ-Opioid agonists are clinically effective analgesics, but also produce undesirable effects such as sedation and abuse potential that limit their clinical utility. Glutamatergic systems also modulate nociception and N-methyl D-aspartate (NMDA) receptor antagonists have been proposed as one useful adjunct to enhance the therapeutic effects and/or attenuate the undesirable effects of μ-opioid agonists. Whether NMDA antagonists enhance the antiallodynic effects of μ-agonists in preclinical models of thermal hypersensitivity (i...
December 12, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29239212/sarcoma-family-kinase-activity-is-required-for-cortical-spreading-depression
#3
Fan Bu, Yan Wang, Liwen Jiang, Dongqing Ma, John P Quinn, Minyan Wang
Objectives Sarcoma family kinase activity is associated with multiple diseases including ischemia and cancer; however, its role in the mechanism of migraine aura has been less well characterised. This study aims to investigate whether sarcoma family kinase is required for cortical spreading depression. Methods Cortical spreading depression was induced by topical application of K+ to the cerebral cortex and was monitored using electrophysiology in rats, and intrinsic optical signal in mouse brain slices. Drugs were perfused into the contralateral cerebral ventricle for pharmacological manipulations in rats...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29236648/a-putative-electrophysiological-biomarker-of-auditory-sensory-memory-encoding-is-sensitive-to-pharmacological-alterations-of-excitatory-inhibitory-balance-in-male-macaque-monkeys
#4
William B Holliday, Kate Gurnsey, Robert A Sweet, Tobias Teichert
BACKGROUND: The amplitude of the auditory evoked N1 component that can be derived from noninvasive electroencephalographic recordings increases as a function of time between subsequent tones. N1 amplitudes in individuals with schizophrenia saturate at a lower asymptote, thus giving rise to a reduced dynamic range. Reduced N1 dynamic range is a putative electrophysiological biomarker of altered sensory memory function in individuals with the disease. To date, it is not clear what determines N1 dynamic range and what causes reduced N1 dynamic range in individuals with schizophrenia...
December 13, 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29232014/mutations-of-the-glycine-cleavage-system-genes-possibly-affect-the-negative-symptoms-of-schizophrenia-through-metabolomic-profile-changes
#5
Akane Yoshikawa, Fumichika Nishimura, Aya Inai, Yosuke Eriguchi, Masaki Nishioka, Atsuhiko Takaya, Mamoru Tochigi, Yoshiya Kawamura, Tadashi Umekage, Kayoko Kato, Tsukasa Sasaki, Yoshiaki Ohashi, Kazuya Iwamoto, Kiyoto Kasai, Chihiro Kakiuchi
AIM: Hypofunction of N-methyl-D-aspartate receptors (NMDARs) may contribute to the pathophysiology of schizophrenia (SCZ). Recently, the glycine cleavage system (GCS) was shown to affect NMDAR function in the brain. GCS functional defects cause nonketotic hyperglycinemia (NKH), the atypical phenotype of which presents psychiatric symptoms similar to SCZ. Here, we examined the involvement of GCS in SCZ. METHODS: First, to identify the rare variants and the exonic deletions, we re-sequenced all the coding exons and the splice sites of four GCS genes (GLDC, AMT, GCSH, DLD) in 474 patients with SCZ and 475 controls and performed multiplex ligation-dependent probe amplification (MLPA) analysis in SCZ...
December 12, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29230960/ciq-a-positive-allosteric-modulator-of-glun2c-d-containing-n-methyl-d-aspartate-receptors-rescues-striatal-synaptic-plasticity-deficit-in-a-mouse-model-of-parkinson-s-disease
#6
Mona Nouhi, Xiaoqun Zhang, Ning Yao, Karima Chergui
AIMS: To investigate if CIQ, a positive allosteric modulator of N-methyl-d-aspartate receptors (NMDARs) containing GluN2C/D subunits, rescues the loss of long-term potentiation (LTP) and forelimb-use asymmetry in a mouse model of Parkinson's disease (PD). METHODS: We have used electrophysiology in brain slices and the cylinder test to examine the effect of CIQ on glutamatergic synaptic transmission, synaptic plasticity, and forelimb-use in the unilateral 6-hydroxydopamine-lesion mouse model of PD...
December 11, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29229209/randomized-double-blind-placebo-controlled-dose-escalation-study-investigation-of-the-safety-pharmacokinetics-and-antihyperalgesic-activity-of-l-4-chlorokynurenine-in-healthy-volunteers
#7
Mark Wallace, Alexander White, Kathy A Grako, Randal Lane, Allen Jo Cato, H Ralph Snodgrass
BACKGROUND AND AIMS: Neuropathic pain is a significant medical problem needing more effective treatments with fewer side effects. Overactive glutamatergic transmission via N-methyl-d-aspartate receptors (NMDARs) are known to play a role in central sensitization and neuropathic pain. Although ketamine, a NMDAR channel-blocking antagonist, is often used for neuropathic pain, its side-effect profile and abusive potential has prompted the search for a safer effective oral analgesic. A novel oral prodrug, AV-101 (l-4 chlorokynurenine), which, in the brain, is converted into one of the most potent and selective GlyB site antagonists of the NMDAR, has been demonstrated to be active in animal models of neuropathic pain...
October 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29226117/pediatric-anti-n-methyl-d-aspartate-receptor-encephalitis-a-review-with-pooled-analysis-and-critical-care-emphasis
#8
REVIEW
Kenneth E Remy, Jason W Custer, Joshua Cappell, Cortney B Foster, Nan A Garber, L Kyle Walker, Liliana Simon, Dayanand Bagdure
Purpose: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is being recognized with increasing frequency among children. Given the paucity of evidence to guide the critical care management of these complex patients, we provide a comprehensive review of the literature with pooled analysis of published case reports and case series. Methods: We performed a comprehensive literature search using PubMed, Scopus, EMBASE, and Web of Science for relevant published studies...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29225568/age-dependent-subunit-specific-action-of-hydrogen-sulfide-on-glun1-2a-and-glun1-2b-nmda-receptors
#9
Aleksey V Yakovlev, Evgeniya D Kurmasheva, Yevheniia Ishchenko, Rashid Giniatullin, Guzel F Sitdikova
Hydrogen sulfide (H2S) is an endogenously produced neuroactive gas implicated in many key processes in the peripheral and central nervous system. Whereas the neuroprotective role of H2S has been shown in adult brain, the action of this messenger in newborns remains unclear. One of the known targets of H2S in the nervous system is the N-methyl-D-aspartate (NMDA) glutamate receptor which can be composed of different subunits with distinct functional properties. In the present study, using patch clamp technique, we compared the effects of the H2S donor sodium hydrosulfide (NaHS, 100 μM) on hippocampal NMDA receptor mediated currents in rats of the first and third postnatal weeks...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29225043/neurogranin-in-the-nucleus-accumbens-regulates-nmda-receptor-tolerance-and-motivation-for-ethanol-seeking
#10
Ashlie N Reker, Alfredo Oliveros, John M Sullivan, Lailun Nahar, David J Hinton, Taehyun Kim, Robert C Bruner, Doo-Sup Choi, Nicholas E Goeders, Hyung W Nam
Dysfunction of N-methyl-D-aspartate receptor (NMDAR) signaling in the nucleus accumbens (NAc) has been implicated in the pathophysiology of alcohol use disorders (AUD). Neurogranin (Ng), a calmodulin-binding protein, is exclusively expressed in the post-synapse, and mediates NMDAR driven synaptic plasticity by regulating the calcium-calmodulin (Ca2+-CaM) pathway. To study the functional role of Ng in AUD, we administrated behavior tests including Pavlovian instrument transfer (PIT), operant conditioning, and rotarod test using Ng null mice (Ng-/- mice)...
December 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29225006/mechanistic-studies-on-ketamine-induced-mitochondrial-toxicity-in-zebrafish-embryos
#11
Bonnie L Robinson, Melanie Dumas, Syed F Ali, Merle G Paule, Qiang Gu, Jyotshna Kanungo
Ketamine, a phencyclidine derivative, is an antagonist of the Ca2+-permeable N-methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells. Our previous studies showed that acetyl l-carnitine (ALCAR) prevented ketamine-induced cardiotoxicity and neurotoxicity in zebrafish embryos. Based on our finding that ALCAR's protective effect was blunted by oligomycin A, an inhibitor of ATP synthase, we further investigated the effects of ketamine and ALCAR on ATP levels, mitochondria and ATP synthase in zebrafish embryos...
December 7, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29223589/breakthroughs-in-neuroactive-steroid-drug-discovery
#12
REVIEW
Maria-Jesus Blanco, Daniel La, Quinn Coughlin, Caitlin A Newman, Andrew M Griffin, Boyd L Harrison, Francesco G Salituro
Endogenous and synthetic neuroactive steroids (NASs) or neurosteroids are effective modulators of multiple signaling pathways including receptors for the γ-aminobutyric acid A (GABAA) and glutamate, in particular N-methyl-d-aspartate (NMDA). These receptors are the major inhibitory and excitatory neurotransmitters in the central nervous system (CNS), and there is growing evidence suggesting that dysregulation of neurosteroid production plays a role in numerous neurological disorders. The significant unmet medical need for treatment of CNS disorders has increased the interest for these types of compounds...
December 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29222517/input-dependent-regulation-of-excitability-controls-dendritic-maturation-in-somatosensory-thalamocortical-neurons
#13
Laura Frangeul, Vassilis Kehayas, Jose V Sanchez-Mut, Sabine Fièvre, K Krishna-K, Gabrielle Pouchelon, Ludovic Telley, Camilla Bellone, Anthony Holtmaat, Johannes Gräff, Jeffrey D Macklis, Denis Jabaudon
Input from the sensory organs is required to pattern neurons into topographical maps during development. Dendritic complexity critically determines this patterning process; yet, how signals from the periphery act to control dendritic maturation is unclear. Here, using genetic and surgical manipulations of sensory input in mouse somatosensory thalamocortical neurons, we show that membrane excitability is a critical component of dendritic development. Using a combination of genetic approaches, we find that ablation of N-methyl-D-aspartate (NMDA) receptors during postnatal development leads to epigenetic repression of Kv1...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29209138/effects-of-glutathione-on-mechanical-allodynia-and-central-sensitization-in-chronic-postischemic-pain-rats
#14
Jinseok Yeo, Hoon Jung, Hyerim Lee
Background: The chronic postischemia pain (CPIP) model is an animal model using ischemia/reperfusion injury that mimics the symptoms of complex regional pain syndrome type I. Glutathione (GSH) prevents ischemia/reperfusion injury by scavenging free radicals. We conducted this study to investigate the protective effect of GSH in CPIP rats via changes of mechanical allodynia and phospholyration of the N-methyl-D-aspartate receptor subunit GluN1. Methods: We divided 45 rats into 5 groups: sham, CPIP, CPIP + GSH 100 mg/kg, CPIP + GSH 200 mg/kg, and CPIP + GSH 500 mg/kg...
2017: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/29207398/involvement-of-n-methyl-d-aspartic-acid-receptor-and-dl-%C3%AE-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid-receptor-in-ginsenosides-rb1-and-rb3-against-oxygen-glucose-deprivation-induced-injury-in-hippocampal-slices-from-rat
#15
Shan Jiang, De-Fang Fang, Ying Chen
OBJECTIVE: Ginsenosides, Rb1 and Rb3, are the major protopanaxadiol components of ginseng saponin. In the present study, the influences of ginsenosides Rb1 and Rb3 on N-methyl-D-aspartic acid (NMDA) receptor or DL-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated synaptic transmission after oxygen-glucose deprivation (OGD) were investigated. METHODS: NMDA receptor population spike (NMDA-PS) or AMPA receptor-mediated population spike (AMPA-PS) was recorded in the CA1 pyramidal cell layer of rat hippocampal slices by electrophysiological techniques...
December 5, 2017: Pharmacology
https://www.readbyqxmd.com/read/29207018/clinical-significance-of-interleukin%C3%A2-6-and-inducible-nitric-oxide-synthase-in-ketamine%C3%A2-induced-cystitis
#16
Chi-Jung Huang, Fa-Kung Lee, Shao-Kuan Chen, Chih-Cheng Chien, Sheng-Tang Wu, Yen-Chieh Wang
Ketamine is an ionotropic glutamatergic N‑methyl‑D‑aspartate receptor antagonist, which is widely used among recreational drug abusers. Ketamine abusers exhibit substantially reduced bladder capacity, which can lead to urinary frequency. The molecular pathogenesis of ketamine‑induced cystitis has been scarcely reported. Given previous clinical findings, it may be hypothesized that pathological alterations in smooth muscle cells (SMCs) of the urinary bladder serve a crucial role in the mechanism underlying cystitis...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29205667/the-effect-of-postnatal-manganese-exposure-on-the-nmda-receptor-signaling-pathway-in-rat-hippocampus
#17
Lei Wang, HuanHuan Fu, Bin Liu, XiaoYan Liu, WeiWei Chen, XiaoDan Yu
Overexposure to manganese (Mn) is associated with neurological disorders in children. Evidence indicated that N-methyl-d-aspartate (NMDA) receptor signaling pathway was critical for neurobehavioral function. However, whether NMDA receptor signaling pathway contributes to Mn-induced neurotoxicity remains unknown. In this study, newborn Sprague-Dawley rats were randomly assigned to four groups exposed to 0, 10, 20, and 30 mg/kg of Mn2+ by intraperitoneal injection (n = 10/group: five males and five females)...
December 4, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29205034/augmentation-of-anticancer-drug-efficacy-in-murine-hepatocellular-carcinoma-cells-by-a-peripherally-acting-competitive-n-methyl-d-aspartate-nmda-receptor-antagonist
#18
Mikko Gynther, Ilaria Proietti Silvestri, Jacob C Hansen, Kasper B Hansen, Tarja Malm, Yevheniia Ishchenko, Younes Larsen, Liwei Han, Silke Kayser, Seppo Auriola, Aleksanteri Petsalo, Birgitte Nielsen, Darryl S Pickering, Lennart Bunch
The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure-activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying biological mechanism was shown to be interference with the lipid signaling pathway, leading to reduced expression of MDR transporters and thereby an increased accumulation of sorafenib in the cancer cells...
December 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29203848/bdnf-release-and-signaling-are-required-for-the-antidepressant-actions-of-glyx-13
#19
T Kato, M V Fogaça, S Deyama, X-Y Li, K Fukumoto, R S Duman
Conventional antidepressant medications, which act on monoaminergic systems, display significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. GLYX-13 is a novel glutamatergic compound that acts as an N-methyl-d-aspartate (NMDA) modulator with glycine-like partial agonist properties; like the NMDA receptor antagonist ketamine GLYX-13 produces rapid antidepressant actions in depressed patients and in preclinical rodent models. However, the mechanisms underlying the antidepressant actions of GLYX-13 have not been characterized...
December 5, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29203399/anti-thyroid-antibodies-and-thyroid-function-in-anti-n-methyl-d-aspartate-receptor-encephalitis
#20
Yinyao Lin, Sha Tan, Yuge Wang, Xianru Shen, Yaqin Shu, Yilong Shan, Yanqiang Wang, Haiyan Li, Lei Zhang, Wei Cai, Xiaobo Sun, Zhengqi Lu
No abstract text is available yet for this article.
December 1, 2017: Neurochemistry International
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