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GluN2B

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https://www.readbyqxmd.com/read/29766293/nmda-receptor-subunits-change-in-the-prefrontal-cortex-of-pure-opioid-and-multi-drug-abusers-a-post-mortem-study
#1
Hamidreza Daneshparvar, Mitra-Sadat Sadat-Shirazi, Monir Fekri, Solmaz Khalifeh, Ali Ziaie, Nasrin Esfahanizadeh, Nasim Vousooghi, Mohammad-Reza Zarrindast
Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-D-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers...
May 16, 2018: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/29764972/separate-functional-properties-of-nmdars-regulate-distinct-aspects-of-spatial-cognition
#2
Erin M Sanders, Akua O Nyarko-Odoom, Kevin Zhao, Michael Nguyen, Hong Hong Liao, Matthew Keith, Jane Pyon, Alyssa Kozma, Mohima Sanyal, Daniel G McHail, Theodore C Dumas
N -methyl-d-aspartate receptors (NMDARs) at excitatory synapses are central to activity-dependent synaptic plasticity and learning and memory. NMDARs act as ionotropic and metabotropic receptors by elevating postsynaptic calcium concentrations and by direct intracellular protein signaling. In the forebrain, these properties are controlled largely by the auxiliary GluN2 subunits, GluN2A and GluN2B. While calcium conductance through NMDAR channels and intracellular protein signaling make separate contributions to synaptic plasticity, it is not known if these properties individually influence learning and memory...
June 2018: Learning & Memory
https://www.readbyqxmd.com/read/29760525/two-distinct-mechanisms-for-experience-dependent-homeostasis
#3
Michelle C D Bridi, Roberto de Pasquale, Crystal L Lantz, Yu Gu, Andrew Borrell, Se-Young Choi, Kaiwen He, Trinh Tran, Su Z Hong, Andrew Dykman, Hey-Kyoung Lee, Elizabeth M Quinlan, Alfredo Kirkwood
Models of firing rate homeostasis such as synaptic scaling and the sliding synaptic plasticity modification threshold predict that decreasing neuronal activity (for example, by sensory deprivation) will enhance synaptic function. Manipulations of cortical activity during two forms of visual deprivation, dark exposure (DE) and binocular lid suture, revealed that, contrary to expectations, spontaneous firing in conjunction with loss of visual input is necessary to lower the threshold for Hebbian plasticity and increase miniature excitatory postsynaptic current (mEPSC) amplitude...
May 14, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29748616/prion-protein-is-essential-for-the-re1-silencing-transcription-factor-rest-dependent-developmental-switch-in-synaptic-nmda-receptors
#4
Zhiqi Song, Wei Yang, Guangyu Cheng, Xiangmei Zhou, Lifeng Yang, Deming Zhao
It is important that the correct amounts of GluN2 subunits are maintained, as they determine NMDAR functional properties, which are crucial to neuronal communication, synaptogenesis and cognitive function. The transcriptional repressor RE1 silencing transcription factor (REST) is critical for the postnatal developmental switch in NMDARs. However, the mechanisms triggering REST and the link between NMDARs and REST are unclear. Here we show a new physiological essential role for cellular prion protein (PrPC ) in REST-dependent homeostasis and the developmental switch of NMDARs...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29708744/positive-modulators-of-the-n-methyl-d-aspartate-receptor-structure-activity-relationship-study-on-steroidal-3-hemiesters
#5
Barbora Krausova, Barbora Slavikova, Michaela Nekardova, Pavla Hubalkova, Vojtech Vyklicky, Hana Chodounska, Ladislav Vyklicky, Eva Kudova
Here, we report the synthesis of pregn-5-ene and androst-5-ene dicarboxylic acid esters and explore the structure-activity relationship (SAR) for their modulation of N-methyl- D-aspartate receptors (NMDARs). All compounds were positive modulators of recombinant GluN1/GluN2B receptors (EC50 varying from 1.8 to 151.4 µM and Emax varying from 48 to 452 %). Moreover, 10 compounds were found to be more potent GluN1/GluN2B receptor modulators than endogenous pregnenolone sulfate (EC50 = 21.7 µM). The SAR study revealed a relationship between the length of the residues at carbon C-3 of the steroid molecule and the positive modulatory effect at GluN1/GluN2B receptors for various D-ring modifications...
April 30, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29706992/nmda-receptor-subunits-change-after-synaptic-plasticity-induction-and-learning-and-memory-acquisition
#6
REVIEW
María Verónica Baez, Magalí Cecilia Cercato, Diana Alicia Jerusalinsky
NMDA ionotropic glutamate receptors (NMDARs) are crucial in activity-dependent synaptic changes and in learning and memory. NMDARs are composed of two GluN1 essential subunits and two regulatory subunits which define their pharmacological and physiological profile. In CNS structures involved in cognitive functions as the hippocampus and prefrontal cortex, GluN2A and GluN2B are major regulatory subunits; their expression is dynamic and tightly regulated, but little is known about specific changes after plasticity induction or memory acquisition...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29702698/comprehensive-behavioral-analysis-of-the-cdkl5-knockout-mice-revealed-significant-enhancement-in-anxiety-and-fear-related-behaviors-and-impairment-in-both-acquisition-and-long-term-retention-of-spatial-reference-memory
#7
Kosuke Okuda, Keizo Takao, Aya Watanabe, Tsuyoshi Miyakawa, Masashi Mizuguchi, Teruyuki Tanaka
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles...
2018: PloS One
https://www.readbyqxmd.com/read/29700290/brain-region-specific-disruption-of-shank3-in-mice-reveals-a-dissociation-for-cortical-and-striatal-circuits-in-autism-related-behaviors
#8
Alexandra L Bey, Xiaoming Wang, Haidun Yan, Namsoo Kim, Rebecca L Passman, Yilin Yang, Xinyu Cao, Aaron J Towers, Samuel W Hulbert, Lara J Duffney, Erin Gaidis, Ramona M Rodriguiz, William C Wetsel, Henry H Yin, Yong-Hui Jiang
We previously reported a new line of Shank3 mutant mice which led to a complete loss of Shank3 by deleting exons 4-22 (Δe4-22) globally. Δe4-22 mice display robust ASD-like behaviors including impaired social interaction and communication, increased stereotypical behavior and excessive grooming, and a profound deficit in instrumental learning. However, the anatomical and neural circuitry underlying these behaviors are unknown. We generated mice with Shank3 selectively deleted in forebrain, striatum, and striatal D1 and D2 cells...
April 27, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29689373/effects-of-the-nmda-receptor-antagonists-dizocilpine-and-ro-63-1908-on-delay-discounting-and-risky-decision-making-in-a-gambling-task
#9
Guy A Higgins, Leo B Silenieks, Cam MacMillan, Fiona D Zeeb, Sandy Thevarkunnel
Previous studies demonstrated that NMDA receptor antagonists such as dizocilpine (MK801) and the GluN2B NMDA antagonist Ro 63-1908 promote impulsive action (motor impulsivity). The effects of these treatments on impulsive choice and decision-making is less well characterized. Two experiments were undertaken. In the first experiment, given evidence for delay order as a factor in choice selection, the effect of dizocilpine was examined in a delay discounting task with separate groups of male Long-Evans rats trained to a schedule of either ascending (i...
April 21, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29684474/environmental-enrichment-cognitive-neuroprotection-in-an-experimental-model-of-cerebral-ischemia-biochemical-and-molecular-aspects
#10
Lara Vezula Gonçalves, Alice Laschuk Herlinger, Tamara Andrea Alarcon Ferreira, Juliana Barbosa Coitinho, Rita Gomes Wanderley Pires, Cristina Martins-Silva
Stroke is considered a major cause of global morbidity. Currently, there are no effective treatments for post-stroke cognitive impairment. Enriched environment (EE) has been brought forward as a preconditioning method to induce cerebral tolerance in an ischemic event. However, the subjacent mechanisms involved in this tolerance are not yet clear. Herein we aimed to identify the mechanisms of neuroprotection triggered by EE preconditioning in a murine model of ischemic stroke. In order to do so, C57Bl/6 mice were kept for five weeks either in EE or in standard environment (SC) prior to ischemic injury through bilateral carotid occlusion (BCCAo) or sham surgery...
April 20, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29682799/the-differences-between-glun2a-and-glun2b-signaling-in-the-brain
#11
REVIEW
Yongjun Sun, Yingge Xu, Xiaokun Cheng, Xi Chen, Yinghua Xie, Linan Zhang, Long Wang, Jie Hu, Zibin Gao
The N-methyl-d-aspartate (NMDA) receptor, a typical ionotropic glutamate receptor, is a crucial protein for maintaining brain function. GluN2A and GluN2B are the main types of NMDA receptor subunit in the adult forebrain. Studies have demonstrated that they play different roles in a number of pathophysiological processes. Although the underlying mechanism for this has not been clarified, the most fundamental reason may be the differences between the signaling pathways associated with GluN2A and GluN2B. With the aim of elucidating the reasons behind the diverse roles of these two subunits, we described the signaling differences between GluN2A and GluN2B from the aspects of C-terminus-associated molecules, effects on typical downstream signaling proteins, and metabotropic signaling...
April 22, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29682629/triheteromeric-nmda-receptors-from-structure-to-synaptic-physiology
#12
David Stroebel, Mariano Casado, Pierre Paoletti
N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that play crucial roles in brain development and synaptic plasticity. They are also therapeutic targets of interest since their dysfunction is associated with multiple neurological and psychiatric disorders. In vivo , NMDARs exist as multiple subtypes that differ in their subunit composition, anatomical distribution, functional properties, as well as signaling capacities. While much is known about diheteromeric NMDARs composed of two GluN1 subunits and two identical GluN2 (or GluN3) subunits, the majority of native NMDARs are triheteromers containing two GluN1 and two different GluN2 (or a combination of GluN2 and GluN3)...
April 2018: Current Opinion in Physiology
https://www.readbyqxmd.com/read/29681798/the-lili-motif-of-m3-s2-linkers-is-a-component-of-the-nmda-receptor-channel-gate
#13
Marek Ladislav, Jiri Cerny, Jan Krusek, Martin Horak, Ales Balik, Ladislav Vyklicky
N-methyl-D-aspartate receptors (NMDARs) mediate excitatory synaptic transmission in the central nervous system, underlie the induction of synaptic plasticity, and their malfunction is associated with human diseases. Native NMDARs are tetramers composed of two obligatory GluN1 subunits and various combinations of GluN2A-D or, more rarely, GluN3A-B subunits. Each subunit consists of an amino-terminal, ligand-binding, transmembrane and carboxyl-terminal domain. The ligand-binding and transmembrane domains are interconnected via polypeptide chains (linkers)...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29681796/surface-expression-function-and-pharmacology-of-disease-associated-mutations-in-the-membrane-domain-of-the-human-glun2b-subunit
#14
Vojtech Vyklicky, Barbora Krausova, Jiri Cerny, Marek Ladislav, Tereza Smejkalova, Bohdan Kysilov, Miloslav Korinek, Sarka Danacikova, Martin Horak, Hana Chodounska, Eva Kudova, Ladislav Vyklicky
N-methyl-D-aspartate receptors (NMDARs), glutamate-gated ion channels, mediate signaling at the majority of excitatory synapses in the nervous system. Recent sequencing data for neurological and psychiatric patients have indicated numerous mutations in genes encoding for NMDAR subunits. Here, we present surface expression, functional, and pharmacological analysis of 11 de novo missense mutations of the human hGluN2B subunit (P553L; V558I; W607C; N615I; V618G; S628F; E657G; G820E; G820A; M824R; L825V) located in the pre-M1, M1, M2, M3, and M4 membrane regions...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29675573/triclosan-evoked-neurotoxicity-involves-nmdar-subunits-with-the-specific-role-of-glun2a-in-caspase-3-dependent-apoptosis
#15
Konrad A Szychowski, Agnieszka Wnuk, Joanna Rzemieniec, Małgorzata Kajta, Teresa Leszczyńska, Anna K Wójtowicz
Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitising products. A number of studies have shown the presence of TCS in different human tissues such as blood, adipose tissue, the liver, brain as well as in breast milk and urine. N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are widely expressed in the central nervous system and which play key roles in excitatory synaptic transmission. There is, however, no data on the involvement of NMDAR subunits in the apoptotic and neurotoxic effects of TCS...
April 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29670280/mechanism-of-nmda-receptor-channel-block-by-mk-801-and-memantine
#16
Xianqiang Song, Morten Ø Jensen, Vishwanath Jogini, Richard A Stein, Chia-Hsueh Lee, Hassane S Mchaourab, David E Shaw, Eric Gouaux
The NMDA (N-methyl-D-aspartate) receptor transduces the binding of glutamate and glycine, coupling it to the opening of a calcium-permeable ion channel 1 . Owing to the lack of high-resolution structural studies of the NMDA receptor, the mechanism by which ion-channel blockers occlude ion permeation is not well understood. Here we show that removal of the amino-terminal domains from the GluN1-GluN2B NMDA receptor yields a functional receptor and crystals with good diffraction properties, allowing us to map the binding site of the NMDA receptor blocker, MK-801...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29666640/investigating-the-interactive-effects-of-sex-steroid-hormones-and-brain-derived-neurotrophic-factor-during-adolescence-on-hippocampal-nmda-receptor-expression
#17
Cushla R McCarthny, Xin Du, YeeWen Candace Wu, Rachel A Hill
Sex steroid hormones have neuroprotective properties which may be mediated by brain-derived neurotrophic factor (BDNF). This study sought to determine the interactive effects of preadolescent hormone manipulation and BDNF heterozygosity (+/- ) on hippocampal NMDA-R expression. Wild-type and BDNF+/- mice were gonadectomised, and females received either 17 β -estradiol or progesterone treatment, while males received either testosterone or dihydrotestosterone (DHT) treatment. Dorsal (DHP) and ventral hippocampus (VHP) were dissected, and protein expression of GluN1, GluN2A, GluN2B, and PSD-95 was assessed by Western blot analysis...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29651654/in-the-telencephalon-glun2c-nmda-receptor-subunit-mrna-is-predominately-expressed-in-glial-cells-and-glun2d-mrna-in-interneurons
#18
Hassan A Alsaad, Nicholas W DeKorver, Zhihao Mao, Shashank M Dravid, Jyothi Arikkath, Daniel T Monaghan
N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the brain with high concentrations in the telencephalon where they modulate synaptic plasticity, working memory, and other functions. While the actions of the predominate GluN2 NMDAR subunits, GluN2A and GluN2B are relatively well understood, the function of GluN2C and GluN2D subunits in the telencephalon is largely unknown. To better understand the possible role of GluN2C subunits, we used fluorescence in situ hybridization (FISH) together with multiple cell markers to define the distribution and type of cells expressing GluN2C mRNA...
April 12, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29626166/cascades-of-homeostatic-dysregulation-promote-incubation-of-cocaine-craving
#19
Junshi Wang, Masago Ishikawa, Yue Yang, Mami Otaka, James Y Kim, George R Gardner, Michael T Stefanik, Mike Milovanovic, Yanhua H Huang, Johannes W Hell, Marina E Wolf, Oliver M Schlüter, Yan Dong
In human drug users, cue-induced drug craving progressively intensifies after drug abstinence, promoting drug relapse. This time-dependent progression of drug craving is recapitulated in rodent models, in which rats exhibit progressive intensification of cue-induced drug seeking after withdrawal from drug self-administration, a phenomenon termed incubation of drug craving. While recent results suggest that functional alterations of the nucleus accumbens (NAc) contribute to incubation of drug craving, it remains poorly understood how NAc function evolves after drug withdrawal to progressively intensify drug seeking...
April 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29614314/glun2b-camkii-mediates-cfa-induced-hyperalgesia-via-hdac4-modified-spinal-cox2-transcription
#20
Cheng-Yuan Lai, Ming-Chun Hsieh, Yu-Cheng Ho, Gin-Den Chen, Dylan Chou, Ting Ruan, An-Sheng Lee, Hsueh-Hsiao Wang, Yat-Pang Chau, Hsien-Yu Peng, Cheng-Hung Lai
Histone deacetylase 4 (HDAC4), which actively shuttles between the nucleus and cytoplasm, is an attractive candidate for a repressor mechanism in epigenetic modification. However, the potential role of HDAC4-dependent epigenetics in the neural plasticity underlying the development of inflammatory pain has not been well established. By injecting complete Freund's adjuvant (CFA) into the hind-paw of Sprague-Dawley rats (200-250 g), we found animals displayed behavioral hyperalgesia was accompanied with HDAC4 phosphorylation and cytoplasmic redistribution in the dorsal horn neurons...
March 31, 2018: Neuropharmacology
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