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GluN2B

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https://www.readbyqxmd.com/read/29339791/the-glun2a-subunit-regulates-neuronal-nmda-receptor-induced-microglia-neuron-physical-interactions
#1
Ukpong B Eyo, Ashley Bispo, Junting Liu, Sruchika Sabu, Rong Wu, Victoria L DiBona, Jiaying Zheng, Madhuvika Murugan, Huaye Zhang, Yamei Tang, Long-Jun Wu
Microglia are known to engage in physical interactions with neurons. However, our understanding of the detailed mechanistic regulation of microglia-neuron interactions is incomplete. Here, using high resolution two photon imaging, we investigated the regulation of NMDA receptor-induced microglia-neuron physical interactions. We found that the GluN2A inhibitor NVPAAM007, but not the GluN2B inhibitor ifenprodil, blocked the occurrence of these interactions. Consistent with the well-known developmental regulation of the GluN2A subunit, these interactions are absent in neonatal tissues...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339324/oscillatory-synchronous-inhibition-in-the-basolateral-amygdala-and-its-primary-dependence-on-nr2a-containing-nmda-receptors
#2
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/29335819/nmda-receptor-glun2-subtypes-control-epileptiform-events-in-the-hippocampus
#3
Pradeep Punnakkal, Deity Dominic
NMDA receptors (NMDARs) play a key role in synaptic plasticity and excitotoxicity. Subtype-specific role of NMDAR in neural disorders is an emerging area. Recent studies have revealed that mutations in NMDARs are a cause for epilepsy. Hippocampus is a known focal point for epilepsy. In hippocampus, expression of the NMDAR subtypes GluN1/GluN2A and GluN1/GluN2B is temporally regulated. However, the pharmacological significance of these subtypes is not well understood in epileptic context/models. To investigate this, epilepsy was induced in hippocampal slices by the application of artificial cerebrospinal fluid that contained high potassium but no magnesium...
January 15, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29307084/glun2b-subunit-of-the-nmda-receptor-the-keystone-of-the-effects-of-alcohol-during-neurodevelopment
#4
Mickaël Naassila, Olivier Pierrefiche
The glutamatergic system plays a central role in both the acute and chronic effects of ethanol. Among all the glutamate receptors the ionotropic NMDA receptors are crucial because of their role in synaptic plasticity. A large body of evidences suggests that short-term and long-term effects of ethanol may change synaptic plasticity via an alteration of the expression of the GluN2B subunit, one constitutive element of the NMDA receptor. The present review is focusing on the role of the GluN2B subunit after ethanol exposure during early life (in utero and adolescence) and also at adulthood...
January 6, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29289890/hydroxymethyl-bioisosteres-of-phenolic-glun2b-selective-nmda-receptor-antagonists-design-synthesis-and-pharmacological-evaluation
#5
Louisa Temme, Bastian Frehland, Dirk Schepmann, Dina Robaa, Wolfgang Sippl, Bernhard Wünsch
Antagonists addressing selectively NMDA receptors containing the GluN2B subunit are of particular interest for the treatment of various neurological disorders including neurodegenerative diseases. With the aim to bioisosterically replace the metabolically labile phenol of 7-amino-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-ols, several analogs were docked into the ifenprodil binding site leading to the hydroxymethyl derivatives 4 as promising candidates. They display the same binding pose as Ro 25-6981 and the same H-bond interactions with Gln110 and Glu236 within the GluN2B subunit...
December 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29285738/developmental-changes-of-synaptic-and-extrasynaptic-nmda-receptor-expression-in-rat-cerebellar-neurons-in-vitro
#6
Dmitry A Sibarov, Yulia D Stepanenko, Ivan V Silantiev, Polina A Abushik, Tatiana V Karelina, Sergei M Antonov
Transient expression of different NMDA receptors (NMDARs) plays a role in development of the cerebellum. Whether similar processes undergo during neuronal differentiation in culture is not clearly understood. We studied NMDARs in cerebellar neurons in cultures of 7 and 21 days in vitro (DIV) using immunocytochemical and electrophysiological approaches. Whereas at 7 DIV, the vast majority of neurons were immunopositive for GluN2 subunits, further synaptoginesis was accompanied by the time-dependent loss of NMDARs...
December 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29258835/the-glun1-glun2b-nmda-receptor-and-metabotropic-glutamate-receptor-1-negative-allosteric-modulator-has-enhanced-neuroprotection-in-a-rat-subarachnoid-hemorrhage-model
#7
Zongyong Zhang, Junke Liu, Cundong Fan, Leilei Mao, Rongxia Xie, Suyun Wang, Mingfeng Yang, Hui Yuan, Xiaoyi Yang, Jingyi Sun, Jian Wang, Jiming Kong, Siluo Huang, Baoliang Sun
Excessive glutamate in cerebrospinal fluid after subarachnoid hemorrhage (SAH) causes excitotoxic damage through calcium overloading and a subsequent apoptotic cascade. GluN1/GluN2B containing N-methyl-Daspartate (NMDA) receptor and metabotropic glutamate receptor 1 (mGluR1) can play a leading role in glutamate-mediated excitotoxicity. Here we report that Ifenprodil (100μM), a negative allosteric modulator (NAM) of GluN1/GluN2B NMDA receptors, and JNJ16259685 (10μM), a NAM of mGluR1, have an additive efficacy against glutamate (100μM)-induced Ca2+ release and cell apoptosis in primary cortical, hippocampal, and cerebellar granule neurons...
December 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29242355/the-bioactive-protein-ligand-conformation-of-glun2c-selective-positive-allosteric-modulators-bound-to-the-nmda-receptor
#8
Thomas Maxwell Kaiser, Steven A Kell, Hirofumi Kusumoto, Gil Shaulsky, Subhrajit Bhattacharya, Matthew P Epplin, Katie L Strong, Eric J Miller, Bryan D Cox, David S Menaldino, Dennis C Liotta, Stephen F Traynelis, Pieter Buys Burger
NMDA receptors are ligand-gated, cation-selective channels that mediate a slow component of excitatory synaptic transmission. Subunit-selective positive allosteric modulators of NMDA receptor function have therapeutically-relevant effects on multiple processes in the brain. A series of pyrrolidinones, such as PYD-106, that selectively potentiate NMDA receptors that contain the GluN2C subunit have structural determinants of activity that reside between the GluN2C amino terminal domain and the GluN2C agonist binding domain, suggesting a unique site of action...
December 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29242136/anxiolytic-effect-of-cpeb1-knockdown-on-the-amygdala-of-a-mouse-model-of-inflammatory-pain
#9
Jiao Yue, Xin-Shang Wang, Yan-Yan Guo, Kai-Yin Zheng, Hai-Yan Liu, Li-Ning Hu, Ming-Gao Zhao, Shui-Bing Liu
Anxiety disorders are a category of mental disorders characterized by feelings of anxiety, stress, and fear attached to various sources. However, their pathogenesis is complicated and has not been fully elucidated. The amygdala is a vital brain region that regulates anxiety and mental disorders. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the extension of the mRNA polyadenylation tail and facilitates the translation of target RNA. CPEB1 is closely related to neuronal diseases, such as Fragile X Syndrome, learning and memory disorders, and chronic pain...
December 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29218821/activity-dependent-control-of-nmda-receptor-subunit-composition-at-hippocampal-mossy-fibre-synapses
#10
Mario Carta, Bettadapura N Srikumar, Adam Gorlewicz, Nelson Rebola, Christophe Mulle
Single neurons express NMDARs with distinct subunit composition and biophysical properties which can be segregated in an input-specific manner. The dynamic control of the heterogeneous distribution of synaptic NMDARs is crucial to control input-dependent synaptic integration and plasticity. In hippocampal CA3 pyramidal cells (CA3 PCs) from mice of both sexes, we found that mossy fibre (Mf) synapses display a markedly lower proportion of GluN2B containing NMDARs than associative/commissural synapses. The mechanism involved in such heterogeneous distribution of GluN2B subunits is not known...
December 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29199132/brainphys%C3%A2-increases-neurofilament-levels-in-cns-cultures-and-facilitates-investigation-of-axonal-damage-after-a-mechanical-stretch-injury-in-vitro
#11
Travis C Jackson, Shawn E Kotermanski, Edwin K Jackson, Patrick M Kochanek
Neurobasal®/B27 is a gold standard culture media used to study primary neurons in vitro. An alternative media (BrainPhys®/SM1) was recently developed which robustly enhances neuronal activity vs. Neurobasal® or DMEM. To the best of our knowledge BrainPhys® has not been explored in the setting of neuronal injury. Here we characterized the utility of BrainPhys® in a model of in vitro mechanical-stretch injury. METHODS/RESULTS: Primary rat cortical neurons were maintained in classic Neurobasal®, or sequentially maintained in Neurocult® followed by BrainPhys® (hereafter simply referred to as "BrainPhys® maintained neurons")...
November 30, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29196318/inactivation-of-nmda-receptors-in-the-ventral-tegmental-area-during-cocaine-self-administration-prevents-glua1-up-regulation-but-with-paradoxical-increases-in-cocaine-seeking-behavior
#12
Daniel Guzman, Maria B Carreira, Allyson K Friedman, Megumi Adachi, Rachael L Neve, Lisa M Monteggia, Ming-Hu Han, Christopher W Cowan, David W Self
Cocaine self-administration increases expression of GluA1 subunits in ventral tegmental area (VTA) dopamine neurons that subsequently enhance the motivation for cocaine. This increase in GluA1 may be dependent on concomitant NMDA receptor (NMDAR) activation during self-administration, similar to cocaine-induced LTP in the VTA. In this study, we used viral-mediated expression of a dominant negative GluN1 subunit (HSV-dnGluN1) in VTA neurons to study the effect of transient NMDAR inactivation on the GluA1 increases induced by chronic cocaine self-administration in male rats...
December 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29191857/evaluation-of-11c-me-nb1-as-a-potential-pet-radioligand-for-measuring-glun2b-containing-nmda-receptors-drug-occupancy-and-receptor-crosstalk
#13
Stefanie D Krämer, Thomas Betzel, Linjing Mu, Ahmed Haider, Adrienne Herde Müller, Anna K Boninsegni, Claudia Keller, Marina Szermerski, Roger Schibli, Bernhard Wünsch, Simon M Ametamey
Clinical and preclinical research with modulators binding to the NMDA receptor GluN2B N-terminal domain (NTD) aim for the treatment of various neurological diseases. However, the interpretation of the results is hampered by the lack of a suitable NMDA PET tracer for assessing the receptor occupancy of candidate drugs. We have developed [11C]Me-NB1 as a PET tracer for imaging GluN1/GluN2B-containing NMDA receptors and used it to investigate in rats the dose-dependent receptor occupancy of eliprodil, a GluN2B NTD modulator...
November 30, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29176858/sepsis-induced-selective-loss-of-nmda-receptors-modulates-hippocampal-neuropathology-in-surviving-septic-mice
#14
Shuibing Zhang, Xueqin Wang, Sha Ai, Wen Ouyang, Yuan Le, Jianbin Tong
BACKGROUND: Sepsis-induced neuroinflammation plays an important role in sepsis-related brain dysfunction. However, the molecules that are targeted during neuroinflammation resulting from sepsis-induced brain dysfunction remain unclear. Herein, we tried to investigate the expression and roles of NMDA receptor subunits during sepsis-related brain dysfunction. METHODS: Sepsis was induced by cecal ligation and perforation (CLP) or by a single intraperitoneal injection of lipopolysaccharide (LPS, 8 mg/kg) in C57BL/6J mice...
2017: PloS One
https://www.readbyqxmd.com/read/29174530/increased-cortical-neuronal-responses-to-nmda-and-improved-attentional-set-shifting-performance-in-rats-following-prebiotic-b-gos%C3%A2-ingestion
#15
Benjamin Gronier, Helene M Savignac, Mathieu Di Miceli, Sherif M Idriss, George Tzortzis, Daniel Anthony, Philip W J Burnet
We have previously shown that prebiotics (dietary fibres that augment the growth of indigenous beneficial gut bacteria) such as Bimuno™ galacto-oligosaccharides (B-GOS®), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat brain. The current investigation examined the functional correlates of these changes in B-GOS®-fed rats by measuring cortical neuronal responses to NMDA using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the attentional set-shifting task. Adult male rats were supplemented with B-GOS® in the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing...
November 21, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29173480/changed-expressions-of-n-methyl-d-aspartate-receptors-in-the-brains-of-rats-and-primary-neurons-exposed-to-high-level-of-fluoride
#16
Na Wei, Yang-Ting Dong, Jie Deng, Ya Wang, Xiao-Lan Qi, Wen-Feng Yu, Yan Xiao, Jian-Jiang Zhou, Zhi-Zhong Guan
Expressions of N-methyl-d-aspartic acid receptors (NMDARs) in the brains of rats and primary neurons exposed to high fluoride were investigated. Sprague-Dawley rats were divided randomly into a fluorosis group (50ppm fluoride in the drinking water for 6 months) and controls (<0.5ppm fluoride) and the offspring from these rats sacrificed on postnatal days 1, 7, 14, 21 and 28. The primary cultured neurons from the hippocampus of neonatal rats were treated with 5 and 50ppm fluoride for 48h. NMDAR subunits at protein or mRNA levels were quantified by Western blotting or real-time PCR...
January 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29171922/less-means-more-the-magnitude-of-synaptic-plasticity-along-the-hippocampal-dorso-ventral-axis-is-inversely-related-to-the-expression-levels-of-plasticity-related-neurotransmitter-receptors
#17
Valentyna Dubovyk, Denise Manahan-Vaughan
The dorsoventral axis of the hippocampus exhibits functional differentiations with regard to (spatial Vs emotional learning) and information retention (rapid encoding Vs long-term storage), as well as its sensitivity to neuromodulation and information received from extrahippocampal structures. The mechanisms that underlie these differentiations remain unclear. Here, we explored neurotransmitter receptor expression along the dorsoventral hippocampal axis and compared hippocampal synaptic plasticity in the CA1 region of the dorsal (DH), intermediate (IH) and ventral hippocampi (VH)...
November 24, 2017: Hippocampus
https://www.readbyqxmd.com/read/29146480/neuroprotection-by-chotosan-a-kampo-formula-against-glutamate-excitotoxicity-involves-the-inhibition-of-glun2b-but-not-glun2a-containing-nmda-receptor-mediated-responses-in-primary-cultured-cortical-neurons
#18
Sachie Sasaki-Hamada, Azusa Suzuki, Emi Sanai, Kinzo Matsumoto, Jun-Ichiro Oka
Chotosan (CTS), a traditional herbal formula called Kampo medicine, was shown to be effective in the treatment of vascular dementia in a clinical study, and exerted protective effects against transient cerebral ischemia-induced cognitive impairment in mice. In the present study, we investigated the neuroprotective effects of CTS using primary cultured rat cortical neurons. CTS (250-1000 μg/mL) inhibited neuronal death induced by 100 μM glutamate. This glutamate-induced neuronal death was blocked by a GluN2B-, but not GluN2A-containing NMDA receptor antagonist...
November 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29127002/post-acquisition-hippocampal-blockade-of-the-nmda-receptor-subunit-glun2a-but-not-glun2b-sustains-spatial-reference-memory-retention
#19
Keisuke Shinohara, Toshimichi Hata
While it has been shown that the blockade of N-methyl-d-aspartate type glutamate receptors (NMDARs) impairs memory acquisition, recent studies have reported that the post-acquisition administration of NMDAR antagonists suppresses spatial memory decay. These findings suggest that NMDARs are important not only for the acquisition of new memories but also for the decay of previously acquired memories. The present study investigated the contributions of specific NMDAR subunits to spatial memory decay using NVP-AAM077 (NVP), an NMDAR antagonist that preferentially binds to GluN2A subunits, and the selective GluN2B blocker Ro 25-6981 (Ro)...
November 7, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29101031/a-deficiency-of-the-glun2c-subunit-of-the-n-methyl-d-aspartate-receptor-is-neuroprotective-in-a-mouse-model-of-ischemic-stroke
#20
Adam Holmes, Ning Zhou, Deborah L Donahue, Rashna Balsara, Francis J Castellino
The N-methyl-d-aspartate receptor (NMDAR) ion channel plays a pivotal role in the pathology of ischemic stroke. The functional receptor consists of two GluN1 subunits (a-h) and two GluN2 subunits (A/B/C/D), the expression of which are spatially and temporally regulated in pathological and physiological conditions. While the role of the GluN2A and GluN2B subunit in ischemic stroke has been well developed, the role of the GluN2C subunit in ischemia is not well understood. Following middle carotid artery occlusion (MCAO), GluN2C(-/-) male mice displayed similar volumes of infarct as wild-type (WT) mice...
October 31, 2017: Biochemical and Biophysical Research Communications
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