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N-methyl-D-aspartate

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https://www.readbyqxmd.com/read/28723598/effects-of-tumor-necrosis-factor-blocker-on-salicylate-induced-tinnitus-in-mice
#1
Juen-Haur Hwang, David Chang-Wei Huang, Yin-Chang Lu, Wei-Shiung Yang, Tien-Chen Liu
OBJECTIVE: Neuroinflammation is considered a novel mechanism for acute tinnitus. Here, we investigated the effects of a tumor necrosis factor (TNF) blocker on the gene expression of inflammatory-cytokine in the cochlea in a tinnitus animal model. METHODS: Enbrel® (30 mg/kg, intraperitoneally (i.p.)) were administrated to the mice with the salicylate induced tinnitus for 3 days. Tinnitus score and mRNA expression levels of TNFR1, TNFR2, and N-methyl-d-aspartate receptor subunit 2B (NR2B) and its downstream regulatory element antagonist modulator (DREAM) in the cochlea of mice were measured and compared to the control...
June 1, 2017: International Tinnitus Journal
https://www.readbyqxmd.com/read/28721398/calcium-stimulated-adenylyl-cyclase-subtype-1-ac1-contributes-to-ltp-in-the-insular-cortex-of-adult-mice
#2
Manabu Yamanaka, Takanori Matsuura, Haili Pan, Min Zhuo
Long-term potentiation (LTP) of synaptic transmission in the central nervous system is a key form of cortical plasticity. The insular cortex (IC) is known to play important roles in pain perception, aversive memory and mood disorders. LTP has been recently reported in the IC, however, the signaling pathway for IC LTP remains unknown. Here, we investigated the synaptic mechanism of IC LTP. We found that IC LTP induced by the pairing protocol was N-methyl-D-aspartate receptors (NMDARs) dependent, and expressed postsynaptically, since paired-pulse ratio (PPR) was not affected...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28719605/extracellular-phosphorylation-of-a-receptor-tyrosine-kinase-controls-synaptic-localization-of-nmda-receptors-and-regulates-pathological-pain
#3
Kenji Hanamura, Halley R Washburn, Sean I Sheffler-Collins, Nan L Xia, Nathan Henderson, Dipti V Tillu, Shayne Hassler, Daniel S Spellman, Guoan Zhang, Thomas A Neubert, Theodore J Price, Matthew B Dalva
Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28712640/resident-calmodulin-primes-nmda-receptors-for-ca-2-dependent-inactivation
#4
Gary J Iacobucci, Gabriela K Popescu
N-methyl-d-aspartate (NMDA) receptors are glutamate- and glycine-gated channels that flux Na(+) and Ca(2+) into postsynaptic neurons during synaptic transmission. The resulting intracellular Ca(2+) transient is essential to physiological and pathological processes related to synaptic development, plasticity, and apoptosis. It also engages calmodulin (CaM) to reduce subsequent NMDA receptor activity in a process known as Ca(2+)-dependent inactivation (CDI). Here, we used whole-cell electrophysiology to measure CDI and computational modeling to dissect the sequence of events that underlies it...
July 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28711909/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#5
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...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711661/mechanisms-of-action-and-clinical-efficacy-of-nmda-receptor-modulators-in-mood-disorders
#6
REVIEW
Mehdi Ghasemi, Cristy Phillips, Atoossa Fahimi, Margaret Windy McNerney, Ahmad Salehi
Although the biogenic amine models have provided meaningful links between clinical phenomena and pharmacological management of with mood disorders (MDs), the onset of action of current treatments is slow and a proportion of individuals fail to adequately respond. A growing number of investigations have focused on the glutamatergic system as a viable target. Herein we review the putative role of N-methyl-D-aspartate (NMDA) signaling in the pathophysiology of MDs. Prompting this focus are several lines of evidence: 1) altered glutamate and NMDA receptor (NMDAR) expression and functioning; 2) antidepressant effects of NMDAR signaling blockers; 3) interaction between conventional therapeutic regimens and NMDAR signaling modulators; 4) biochemical evidence of interaction between monoaminergic system and NMDAR signaling; 5) interaction between neurotrophic factors and NMDAR signaling in mood regulation; 6) cross-talk between NMDAR signaling and inflammatory processes; and 7) antidepressant effects of a number of NMDA modulators in recent clinical trials...
July 12, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28711476/treatment-in-early-psychosis-with-n-acetyl-cysteine-for-6months-improves-low-level-auditory-processing-pilot-study
#7
Chrysa Retsa, Jean-François Knebel, Eveline Geiser, Carina Ferrari, Raoul Jenni, Margot Fournier, Luis Alameda, Philipp S Baumann, Stephanie Clarke, Philippe Conus, Kim Q Do, Micah M Murray
Sensory impairments constitute core dysfunctions in schizophrenia. In the auditory modality, impaired mismatch negativity (MMN) has been observed in chronic schizophrenia and may reflect N-methyl-d-aspartate (NMDA) hypo-function, consistent with models of schizophrenia based on oxidative stress. Moreover, a recent study demonstrated deficits in the N100 component of the auditory evoked potential (AEP) in early psychosis patients. Previous work has shown that add-on administration of the glutathione precursor N-acetyl-cysteine (NAC) improves the MMN and clinical symptoms in chronic schizophrenia...
July 12, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28711472/interactive-effects-of-an-n-methyl-d-aspartate-receptor-antagonist-and-a-nicotinic-acetylcholine-receptor-agonist-on-mismatch-negativity-implications-for-schizophrenia
#8
Holly K Hamilton, Deepak C D'Souza, Judith M Ford, Brian J Roach, Naomi S Kort, Kyung-Heup Ahn, Savita Bhakta, Mohini Ranganathan, Daniel H Mathalon
N-methyl-d-aspartate glutamate receptor (NMDAR) hypofunction has been implicated in the pathophysiology of schizophrenia, including auditory processing abnormalities reflected by the mismatch negativity (MMN) event-related potential component. Evidence suggesting cognitive benefits from nicotine administration, together with the high rate of cigarette use in patients with schizophrenia, has stimulated interest in whether nicotine modulates NMDAR hypofunction. We examined the interactive effects of ketamine, an NMDAR antagonist that produces transient schizophrenia-like neurophysiological effects, and nicotine, a nicotinic acetylcholine receptor (nAChR) agonist, in 30 healthy volunteers to determine whether nicotine prevents or attenuates MMN abnormalities...
July 12, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28709671/mechanism-and-properties-of-positive-allosteric-modulation-of-n-methyl-d-aspartate-receptors-by-6-alkyl-2-naphthoic-acid-derivatives
#9
Kiran Sapkota, Mark W Irvine, Guangyu Fang, Erica S Burnell, Neil Bannister, Arturas Volianskis, Georgia R Culley, Shashank M Dravid, Graham L Collingridge, David E Jane, Daniel T Monaghan
The theory that N-methyl-d-aspartate receptor (NMDAR) hypofunction is responsible for the symptoms of schizophrenia is well supported by many pharmacological and genetic studies. Accordingly, positive allosteric modulators (PAMs) that augment NMDAR signaling may be useful for treating schizophrenia. Previously we have identified several NMDAR PAMs containing a carboxylic acid attached to naphthalene, phenanthrene, or coumarin ring systems. In this study, we describe several functional and mechanistic properties of UBP684, a 2-naphthoic acid derivative, which robustly potentiates agonist responses at each of the four GluN1a/GluN2 receptors and at neuronal NMDARs...
July 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28704275/agonist-e-6837-and-antagonist-sb-271046-of-5-ht6-receptors-both-reverse-the-depressive-like-effect-induced-in-mice-by-subchronic-ketamine-administration
#10
José E Suárez-Santiago, Alfredo Briones-Aranda, Judith Espinosa-Raya, Ofir Picazo
Major depression is one of the most common affective disorders caused by schizophrenia. The administration of N-methyl-D-aspartate receptor antagonists, such as ketamine, can reproduce the negative and affective symptoms of this disorder in animals. Preclinical studies have shown that 5-HT6 receptor (5-HT6R) agonists and antagonists have a considerable antipsychotic response. The aim of the present study was to evaluate the effect of an acute treatment with an agonist, E-6837, and an antagonist, SB-271046, of 5-HT6R on the immobility induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day, intraperitoneal)...
July 12, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28704198/alzheimer-s-disease-as-it-was-in-the-beginning
#11
REVIEW
Stanislav Kozlov, Alexei Afonin, Igor Evsyukov, Andrei Bondarenko
Since Alzheimer's disease was first described in 1907, many attempts have been made to reveal its main cause. Nowadays, two forms of the disease are known, and while the hereditary form of the disease is clearly caused by mutations in one of several genes, the etiology of the sporadic form remains a mystery. Both forms share similar sets of neuropathological and molecular manifestations, including extracellular deposition of amyloid-beta, intracellular accumulation of hyperphosphorylated tau protein, disturbances in both the structure and functions of mitochondria, oxidative stress, metal ion metabolism disorders, impairment of N-methyl-D-aspartate receptor-related signaling pathways, abnormalities of lipid metabolism, and aberrant cell cycle reentry in some neurons...
July 12, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28702665/structural-switch-from-a-multistranded-g-quadruplex-to-single-strands-as-a-consequence-of-point-mutation-in-the-promoter-of-the-human-grin1-gene
#12
Swati Chaudhary, Mahima Kaushik, Ritushree Kukreti, Shrikant Kukreti
A huge number of G-rich sequences forming quadruplexes are found in the human genome, especially in telomeric regions, UTRs, and the promoter regions of a number of genes. One such gene is GRIN1 encoding the NR1 subunit of the N-methyl-d-aspartate receptor (NMDA). Several lines of reports have implicated that attenuated function of NMDA results in schizophrenia, a genetic disorder characterized by hallucinations, delusions, and psychosis. Involvement of the GRIN1 gene in the pathogenesis of schizophrenia has been extensively analysed...
July 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28701927/activation-of-the-creb-c-fos-pathway-during-long-term-synaptic-plasticity-in-the-cerebellum-granular-layer
#13
Daniela Gandolfi, Silvia Cerri, Jonathan Mapelli, Mariarosa Polimeni, Simona Tritto, Marie-Therese Fuzzati-Armentero, Albertino Bigiani, Fabio Blandini, Lisa Mapelli, Egidio D'Angelo
The induction of long-term potentiation and depression (LTP and LTD) is thought to trigger gene expression and protein synthesis, leading to consolidation of synaptic and neuronal changes. However, while LTP and LTD have been proposed to play important roles for sensori-motor learning in the cerebellum granular layer, their association with these mechanisms remained unclear. Here, we have investigated phosphorylation of the cAMP-responsive element binding protein (CREB) and activation of the immediate early gene c-Fos pathway following the induction of synaptic plasticity by theta-burst stimulation (TBS) in acute cerebellar slices...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28701926/glutamate-deregulation-in-ketamine-induced-psychosis-a-potential-role-of-psd95-nmda-receptor-and-pmca-interaction
#14
Malwina Lisek, Bozena Ferenc, Maciej Studzian, Lukasz Pulaski, Feng Guo, Ludmila Zylinska, Tomasz Boczek
Ketamine causes psychotic episodes and is often used as pharmacological model of psychotic-like behavior in animals. There is increasing evidence that molecular mechanism of its action is more complicated than just N-methyl-D-aspartic acid (NMDA) receptor antagonism and involves interaction with the components of calcium homeostatic machinery, in particular plasma membrane calcium pump (PMCA). Therefore, in this study we aimed to characterize brain region-specific effects of ketamine on PMCA activity, interaction with NMDA receptor through postsynaptic density protein 95 (PSD95) scaffolding proteins and glutamate release from nerve endings...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28701225/association-of-schizophrenia-onset-age-and-white-matter-integrity-with-treatment-effect-of-d-cycloserine-a-randomized-placebo-controlled-double-blind-crossover-study
#15
Kazuo Takiguchi, Akihito Uezato, Michio Itasaka, Hidenori Atsuta, Kenji Narushima, Naoki Yamamoto, Akeo Kurumaji, Makoto Tomita, Kazunari Oshima, Kosaku Shoda, Mai Tamaru, Masahito Nakataki, Mitsutoshi Okazaki, Sayuri Ishiwata, Yasuyoshi Ishiwata, Masato Yasuhara, Kunimasa Arima, Tetsuro Ohmori, Toru Nishikawa
BACKGROUND: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time...
July 12, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28698711/anti-n-methyl-d-aspartate-receptor-encephalitis-a-severe-potentially-reversible-autoimmune-encephalitis
#16
REVIEW
Cai-Yun Liu, Jie Zhu, Xiang-Yu Zheng, Chi Ma, Xu Wang
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is potentially lethal, but it is also a treatable autoimmune disorder characterized by prominent psychiatric and neurologic symptoms. It is often accompanied with teratoma or other neoplasm, especially in female patients. Anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum are characteristic features of the disease, thereby suggesting a pathogenic role in the disease. Here, we summarize recent studies that have clearly documented that both clinical manifestations and the antibodies may contribute to early diagnosis and multidisciplinary care...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28694195/hemoglobins-emerging-roles-in-mental-disorders-metabolical-genetical-and-immunological-aspects
#17
REVIEW
Meric A Altinoz, Bahri Ince
Hemoglobin (Hb) expression in the central nervous system is recently shown. Cooccurences of mental disorders (mainly bipolar disorder (BD) and tic disorders) with β- or α-thalassemia trait or erythrocytosis were witnessed, which may be due to peripheral or central hypoxia/hyperoxia or haplotypal gene interactions. β-Globin genes reside at 11p15.5 close to tyrosine hydroxylase, dopamine receptor DRD4 and Brain Derived Neurotrophic Factor, which involve in psychiatric diseases. α-Globin genes reside at 16p13...
July 8, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28688912/inhibition-of-the-kynurenine-pathway-protects-against-reactive-microglial-associated-reductions-in-the-complexity-of-primary-cortical-neurons
#18
Katherine O'Farrell, Eimear Fagan, Thomas J Connor, Andrew Harkin
Brain glia possess the rate limiting enzyme indoleamine 2, 3-dioxygenase (IDO) which catalyses the conversion of tryptophan to kynurenine. Microglia also express kynurenine monooxygenase (KMO) and kynureninase (KYNU) which lead to the production of the free radical producing metabolites, 3-hydroxykynurenine and 3-hydroxyanthranillic acid respectively and subsequently production of the NMDA receptor agonist quinolinic acid. The aim of this study was to examine the effect of IFNγ-stimulated kynurenine pathway (KP) induction in microglia on neurite outgrowth and complexity, and to determine whether alterations could be abrogated using pharmacological inhibitors of the KP...
July 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28688852/cdkl5-controls-postsynaptic-localization-of-glun2b-containing-nmda-receptors-in-the-hippocampus-and-regulates-seizure-susceptibility
#19
Kosuke Okuda, Shizuka Kobayashi, Masahiro Fukaya, Aya Watanabe, Takuto Murakami, Mai Hagiwara, Tempei Sato, Hiroe Ueno, Narumi Ogonuki, Sayaka Komano-Inoue, Hiroyuki Manabe, Masahiro Yamaguchi, Atsuo Ogura, Hiroshi Asahara, Hiroyuki Sakagami, Masashi Mizuguchi, Toshiya Manabe, Teruyuki Tanaka
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA...
July 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28687197/opioid-receptor-activation-is-involved-in-neuroprotection-induced-by-trpv1-channel-activation-against-excitotoxicity-in-the-rat-retina
#20
Kenji Sakamoto, Taiyo Kuroki, Tomonori Sagawa, Hiroko Ito, Asami Mori, Tsutomu Nakahara, Kunio Ishii
Recently, we reported that capsaicin, a transient receptor potential vanilloid type1 (TRPV1) agonist, protected against excitotoxicity induced by intravitreal N-methyl-D-aspartic acid (NMDA) in the rats in vivo. It has been reported that morphine, an opioid receptor agonist, ameliorated excitotoxicity induced by ischemia-reperfusion in the retina, and that capsaicin-induced neuroprotection was reduced by naloxone, an opioid receptor antagonist in the brain. The aim of the present study is to clarify whether activation of opioid receptors is involved in the capsaicin-induced neuroprotection in the retina...
July 4, 2017: European Journal of Pharmacology
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