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https://www.readbyqxmd.com/read/29425730/high-and-low-nightly-running-behavior-associates-with-nucleus-accumbens-n-methyl-d-aspartate-receptor-nmdar-nr1-subunit-expression-and-nmdar-functional-differences
#1
Kolter B Grigsby, Cathleen M Kovarik, George E Rottinghaus, Frank W Booth
The extent to which N-Methyl-D-aspartate (NMDA) receptors facilitate the motivation to voluntarily wheel-run in rodents has yet to be determined. In so, we utilized female Wistar rats selectively bred to voluntarily run high (HVR) and low (LVR) nightly distances in order to examine if endogenous differences in nucleus accumbens (NAc) NMDA receptor expression and function underlies the propensity for high or low motivation to voluntarily wheel-run. 12-14 week old HVR and LVR females were used to examine: 1.) NAc mRNA and protein expression of NMDA subunits NR1, NR2A and NR2B; 2...
February 6, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29423241/novel-rare-variations-in-genes-that-regulate-developmental-change-in-n-methyl-d-aspartate-receptor-in-patients-with-schizophrenia
#2
Akane Yoshikawa, Fumichika Nishimura, Aya Inai, Yosuke Eriguchi, Masaki Nishioka, Atsuhiko Takaya, Mamoru Tochigi, Yoshiya Kawamura, Tadashi Umekage, Kayoko Kato, Tsukasa Sasaki, Kiyoto Kasai, Chihiro Kakiuchi
The mechanism underlying the vulnerability to developing schizophrenia (SCZ) during adolescence remains elusive. Hypofunction of N-methyl-d-aspartate receptors (NMDARs) has been implicated in the pathophysiology of SCZ. During development, the composition of synaptic NMDARs dramatically changes from NR2B-containing NMDARs to NR2A-containing NMDARs through the phosphorylation of NR2B S1480 or Y1472 by CDK5, CSNK2A1, and EphB2, which plays a pivotal role in the maturation of neural circuits. We hypothesized that the dysregulation of developmental change in NMDARs could be involved in the onset of SCZ...
2018: Human Genome Variation
https://www.readbyqxmd.com/read/29382619/the-effects-of-memantine-on-glutamic-receptor-associated-nitrosative-stress-in-a-traumatic-brain-injury-rat-model
#3
Che-Chuan Wang, Hsiao-Yue Wee, Chiao-Ya Hu, Chung-Ching Chio, Jinn-Rung Kuo
BACKGROUND: The main aim of this study is to elucidate whether the neuroprotective effect of memantine, a non-competitive NMDA receptor 2B (NR2B) antagonist, affect neuronal nitrosative stress, apoptosis, and NR2B expression and ultimately improve functional outcomes. MATERIAL AND METHODS: Immediately after the onset of fluid percussion TBI, anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI +vehicle, and TBI+Memantine groups. TBI rats were treated with a memantine intraperitoneal injection dose of 20 mg/kg i...
January 27, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29364283/a-simple-cell-based-immunofluorescence-assay-to-detect-autoantibody-against-the-n-methyl-d-aspartate-nmda-receptor-in-blood
#4
Chia-Hsiang Chen, Yu-Syuan Chang
The presence of anti-NMDA receptor autoantibody can cause various neuropsychiatric symptoms in the affected patients, termed anti-NMDA receptor autoimmune encephalitis. Detection of the specific autoantibody against the NMDA receptor in the blood or cerebrospinal fluid (CSF) is essential for the accurate diagnosis of this condition. The NMDA receptor is an ion channel protein complex that contains four subunits, including two mandatory NMDA receptor subunit 1 (NR1) and one or two NMDA receptor subunit 2A (NR2A), NMDA receptor subunit 2B (NR2B), NMDA receptor subunit 2C (NR2C), or NMDA receptor subunit 2D (NR2D)...
January 9, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29339324/oscillatory-synchronous-inhibition-in-the-basolateral-amygdala-and-its-primary-dependence-on-nr2a-containing-nmda-receptors
#5
Vassiliki Aroniadou-Anderjaska, Volodymyr I Pidoplichko, Taiza H Figueiredo, Maria F M Braga
Synchronous, rhythmic firing of GABAergic interneurons is a fundamental mechanism underlying the generation of brain oscillations, and evidence suggests that NMDA receptors (NMDARs) play a key role in oscillatory activity by regulating the activity of interneurons. Consistent with this, derangement of brain rhythms in certain neuropsychiatric disorders, notably schizophrenia and autism, is associated with NMDAR hypofunction and loss of inhibitory interneurons. In the basolateral amygdala (BLA)-dysfunction of which is involved in a host of neuropsychiatric diseases-, principal neurons display spontaneous, rhythmic "bursts" of inhibitory activity, which could potentially be involved in the orchestration of oscillations in the BLA network; here, we investigated the role of NMDARs in these inhibitory oscillations...
January 12, 2018: Neuroscience
https://www.readbyqxmd.com/read/29305627/antagonism-at-the-nr2b-subunit-of-nmda-receptors-induces-increased-connectivity-of-the-prefrontal-and-subcortical-regions-regulating-reward-behavior
#6
Natalia Gass, Robert Becker, Markus Sack, Adam J Schwarz, Jonathan Reinwald, Alejandro Cosa-Linan, Lei Zheng, Christian Clemm von Hohenberg, Dragos Inta, Andreas Meyer-Lindenberg, Wolfgang Weber-Fahr, Peter Gass, Alexander Sartorius
RATIONALE: Evidence indicates that ketamine's rapid antidepressant efficacy likely results from its antagonism of NR2B-subunit-containing NMDA receptors (NMDAR). Since ketamine equally blocks NR2A- and NR2B-containing NMDAR, and has affinity to other receptors, NR2B-selective drugs might have improved therapeutic efficiency and side effect profile. OBJECTIVES: We aimed to compare the effects of (S)-ketamine and two different types of NR2B-selective antagonists on functional brain networks in rats, in order to find common circuits, where their effects intersect, and that might explain their antidepressant action...
January 5, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29241709/regulation-of-pleiotrophin-and-fyn-in-the-striatum-of-rats-undergoing-l-dopa-induced-dyskinesia
#7
Gimena Gomez, Mariano D Saborido, María A Bernardi, Oscar S Gershanik, Irene R Taravini, Juan E Ferrario
L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats...
December 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29241651/distinct-roles-of-prelimbic-and-infralimbic-probdnf-in-extinction-of-conditioned-fear
#8
Wei Sun, Xiaoliang Li, Lei An
Brain-derived neurotrophic factor (BDNF) has been investigated for its positive role in regulation of fear acquisition and memory. The precursor of BDNF, proBDNF, has been identified as different protein from its mature form. The prelimbic (PL) and infralimbic (IL) sub-regions of the medial prefrontal cortex (mPFC) are functionally distinct in fear behavior. However, the role of PL and IL proBDNF in fear memory is unclear. Here, through the infusion of cleavage-resistant proBDNF and its antibody, we identified the dissociable roles of PL and IL proBDNF in fear expression and extinction memory as well as explored proBDNF's potential mechanism of action...
December 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29205667/the-effect-of-postnatal-manganese-exposure-on-the-nmda-receptor-signaling-pathway-in-rat-hippocampus
#9
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/29187078/maternal-fluoride-exposure-during-gestation-and-lactation-decreased-learning-and-memory-ability-and-glutamate-receptor-mrna-expressions-of-mouse-pups
#10
Z Sun, Y Zhang, X Xue, R Niu, J Wang
Previous investigations demonstrated that high fluoride (F) exposure may adversely affect the neurodevelopment and learning and memory ability. However, whether maternal F exposure during gestation and lactation can influence the learning, memory ability, and glutamate receptor expressions of offspring has not yet been elucidated. Hence, in the present study, maternal mice were exposed to F (25, 50, or 100 mg/L sodium fluoride (NaF) in drinking water) during gestation and lactation. Results showed that exposure to 100 mg/L NaF significantly enhanced the number of total arm entries and working memory errors of offspring in the radial arm maze test compared to the control group...
January 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29185359/gualou-guizhi-decoction-reverses-brain-damage-with-cerebral-ischemic-stroke-multi-component-directed-multi-target-to-screen-calcium-overload-inhibitors-using-combination-of-molecular-docking-and-protein-protein-docking
#11
Juan Hu, Wen-Sheng Pang, Jing Han, Kuan Zhang, Ji-Zhou Zhang, Li-Dian Chen
Stroke is a disease of the leading causes of mortality and disability across the world, but the benefits of drugs curative effects look less compelling, intracellular calcium overload is considered to be a key pathologic factor for ischemic stroke. Gualou Guizhi decoction (GLGZD), a classical Chinese medicine compound prescription, it has been used to human clinical therapy of sequela of cerebral ischemia stroke for 10 years. This work investigated the GLGZD improved prescription against intracellular calcium overload could decreased the concentration of [Ca2+]i in cortex and striatum neurone of MCAO rats...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29167323/prefrontal-cortical-specific-differences-in-behavior-and-synaptic-plasticity-between-adolescent-and-adult-mice
#12
Xanthippi Konstantoudaki, Kleanthi Chalkiadaki, Elisavet Vasileiou, Katerina Kalemaki, Domna Karagogeos, Kyriaki Sidiropoulou
Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC , particularly compared to other primary cortical areas...
November 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29161964/suicidal-ideation-in-systemic-lupus-erythematosus-nr2a-gene-polymorphism-clinical-and-psychosocial-factors
#13
R I Buji, N A Abdul Murad, L F Chan, T Maniam, M S Mohd Shahrir, M Rozita, A S Shamsul, R Mohamad Hussain, N Abdullah, R Jamal, N R Nik Jaafar
Background Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/29139560/the-mammalian-circadian-clock-exhibits-chronic-ethanol-tolerance-and-withdrawal-induced-glutamate-hypersensitivity-accompanied-by-changes-in-glutamate-and-trkb-receptor-proteins
#14
Jonathan H Lindsay, Rebecca A Prosser
BACKGROUND: Alcohol tolerance and withdrawal-induced effects are criteria for alcohol use disorders listed by the DSM-V. Although tolerance and withdrawal have been studied over many decades, there is still uncertainty regarding mechanistic distinctions that characterize these different forms of ethanol (EtOH)-induced plasticity. Previously, we demonstrated that the suprachiasmatic nucleus (SCN) circadian clock develops both acute and rapid tolerance to EtOH inhibition of glutamate-induced circadian phase shifts...
November 15, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29114206/controversial-effects-of-d-amino-acid-oxidase-activator-daoa-g72-on-d-amino-acid-oxidase-dao-activity-in-human-neuronal-astrocyte-and-kidney-cell-lines-the-n-methyl-d-aspartate-nmda-receptor-hypofunction-point-of-view
#15
Vinita Jagannath, Zacharias Faidon Brotzakis, Michele Parrinello, Susanne Walitza, Edna Grünblatt
Dysfunction of D-amino acid oxidase (DAO) and DAO activator (DAOA)/G72 genes have been linked to neuropsychiatric disorders. The glutamate hypothesis of schizophrenia has proposed that increased DAO activity leads to decreased D-serine, which subsequently may lead to N-methyl-D-aspartate (NMDA) receptor hypofunction. It has been shown that DAOA binds to DAO and increases its activity. However, there are also studies showing DAOA decreases DAO activity. Thus, the effect of DAOA on DAO is controversial. We aimed to understand the effect of DAOA on DAO activity in neuron-like (SH-SY5Y), astrocyte-like (1321N1) and kidney-like (HEK293) human cell lines...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29099938/nyx-2925-is-a-novel-nmda-receptor-specific-spirocyclic-%C3%AE-lactam-that-modulates-synaptic-plasticity-processes-associated-with-learning-and-memory
#16
M Amin Khan, David R Houck, Amanda L Gross, Xiao-Lei Zhang, Cassia Cearley, Torsten M Madsen, Roger A Kroes, Patric K Stanton, Jeffrey Burgdorf, Joseph R Moskal
Background: N-methyl-D-aspartate receptors (NMDAR) are one member of a family of ionotropic glutamate receptors that play a pivotal role in synaptic plasticity processes associated with learning and have become attractive therapeutic targets for diseases such as depression, anxiety, schizophrenia, and neuropathic pain. NYX-2925 ((2S, 3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide) is one member of a spiro--lactam-based chemical platform that mimics some of the dipyrrolidine structural features of rapastinel (formerly GLYX-13: threonine-proline-proline-threonine) and is distinct from known NMDAR agonists or antagonists such as D-cycloserine, ketamine, MK-801, kynurenic acid or ifenprodil...
November 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29075536/neural-plasticity-associated-with-hippocampal-pka-creb-and-nmda-signaling-is-involved-in-the-antidepressant-effect-of-repeated-low-dose-of-yueju-pill-on-chronic-mouse-model-of-learned-helplessness
#17
Zhilu Zou, Yin Chen, Qinqin Shen, Xiaoyan Guo, Yuxuan Zhang, Gang Chen
Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29075179/bdnf-val66met-polymorphism-impairs-hippocampal-long-term-depression-by-down-regulation-of-5-ht3-receptors
#18
Rui Hao, Yu Qi, Dong-Ni Hou, Yuan-Yuan Ji, Chun-Yan Zheng, Chu-Yu Li, Wing-Ho Yung, Bai Lu, Ying Huang
Brain-derived neurotrophic factor (BDNF) is a key regulator of neuronal plasticity and cognitive functions. BDNF val66met polymorphism, a human single-nucleotide polymorphism (SNP) in the pro-domain of BDNF gene, is associated with deficits in activity-dependent BDNF secretion and hippocampus-dependent memory. However, the underlying mechanism remains unclear. Here we show that in the BDNF(Met/Met) mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. There was a reduction in the total number of cells in hippocampal CA1 region, while hippocampal expression of mRNAs for NR2a, 2b, GluR1, 2 and GABAARβ3 subunits were up-regulated...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29029433/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#19
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...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29022871/a-postmortem-analysis-of-nmda-ionotropic-and-group-1-metabotropic-glutamate-receptors-in-the-nucleus-accumbens-in-schizophrenia
#20
Jeremy S Lum, Samuel J Millard, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
BACKGROUND: The nucleus accumbens (NAcc) has been implicated in the pathology and treatment of schizophrenia. Recent postmortem evidence suggests a hyperglutamatergic state in the NAcc. With the present study we aimed to explore possible glutamatergic alterations in the NAcc of a large schizophrenia cohort. METHODS: We performed immunoblots on postmortem NAcc samples from 30 individuals who had schizophrenia and 30 matched controls. We examined the protein expression of primary glutamatergic receptors, including the N-methyl-D-aspartate (NMDA) receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate receptor (mGluR1 and mGluR5; dimeric and monomeric forms)...
October 6, 2017: Journal of Psychiatry & Neuroscience: JPN
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