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GluN2A

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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/29758384/disruption-of-shp1-nmda-receptor-signaling-in-spinal-cord-dorsal-horn-alleviated-inflammatory-pain
#3
Li Yang, Hu-Hu Bai, Zi-Yang Zhang, Jiang-Ping Liu, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Src-homology 2 domain-containing protein tyrosine phosphatase-1 (SHP1) is one of the non-receptor-like phosphatases that are highly enriched in hematopoietic cells. Although accumulating evidence has implicated the protein tyrosine phosphatases in the regulation of nociceptive transmission and plasticity, it is largely unknown whether SHP1 was expressed in pain-related spinal cord dorsal horn and engaged in the synaptic modification of nociceptive signals. Here we found that SHP1 was present in spinal neurons of rats and functionally coupled to GluN2A subunit-containing N-methyl-d-aspartate subtype of glutamate receptors, one of the key players in central sensitization of nociceptive behaviors...
April 30, 2018: Neuropharmacology
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/29706992/nmda-receptor-subunits-change-after-synaptic-plasticity-induction-and-learning-and-memory-acquisition
#5
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/29684474/environmental-enrichment-cognitive-neuroprotection-in-an-experimental-model-of-cerebral-ischemia-biochemical-and-molecular-aspects
#6
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
#7
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
#8
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
#9
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/29675573/triclosan-evoked-neurotoxicity-involves-nmdar-subunits-with-the-specific-role-of-glun2a-in-caspase-3-dependent-apoptosis
#10
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/29666640/investigating-the-interactive-effects-of-sex-steroid-hormones-and-brain-derived-neurotrophic-factor-during-adolescence-on-hippocampal-nmda-receptor-expression
#11
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/29666360/signaling-pathways-responsible-for-the-rapid-antidepressant-like-effects-of-a-glun2a-preferring-nmda-receptor-antagonist
#12
Marta Gordillo-Salas, Fuencisla Pilar-Cuéllar, Yves P Auberson, Albert Adell
In a previous study we found that the preferring GluN2A receptor antagonist, NVP-AAM077, elicited rapid antidepressant-like effects in the forced swim test that was related to the release of glutamate and serotonin in the medial prefrontal cortex. In the present work we sought to examine the duration of this behavioral effect as well as the molecular readouts involved. Our results showed that NVP-AAM077 reduced the immobility in the forced swim test 30 min and 24 h after its administration. However, this effect waned 7 days later...
April 18, 2018: Translational Psychiatry
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
#13
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/29644724/a-novel-missense-mutation-in-grin2a-causes-a-nonepileptic-neurodevelopmental-disorder
#14
Ana Fernández-Marmiesse, Hirofumi Kusumoto, Saray Rekarte, Iria Roca, Jin Zhang, Scott J Myers, Stephen F Traynelis, Mª Luz Couce, Luis Gutierrez-Solana, Hongjie Yuan
BACKGROUND: Mutations in the GRIN2A gene, which encodes the GluN2A (glutamate [NMDA] receptor subunit epsilon-1) subunit of the N-methyl-d-aspartate receptor, have been identified in patients with epilepsy-aphasia spectrum disorders, idiopathic focal epilepsies with centrotemporal spikes, and epileptic encephalopathies with severe developmental delay. However, thus far, mutations in this gene have not been associated with a nonepileptic neurodevelopmental disorder with dystonia. OBJECTIVES: The objective of this study was to identify the disease-causing gene in 2 siblings with neurodevelopmental and movement disorders with no epileptiform abnormalities...
April 11, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29595074/alleviation-of-hippocampal-endoplasmic-reticulum-stress-by-allomyrina-dichotoma-larvae-extract
#15
Jongwan Kim, Md Nazmul Haque, Tae-Won Goo, Il Soo Moon
In the brain, endoplasmic reticulum (ER) stress results in synaptic dysfunction and eventually leads to neurodegeneration. Allomyrina dichotoma larvae are a Chinese ethnomedicine and are widely used in East Asia. In the present study, we investigated the ability of ethanol extract of A. dichotoma larvae (ADE) to improve synaptic structure and function by activating unfolded protein response (UPR) under ER stress in animal and neuron culture models. ER stress was induced in obese mice fed a high fat diet (HFD) or by treating dissociated cultures of rat embryonic (E19) hippocampal neurons with tunicamycin (TM)...
March 29, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29593052/long-term-depression-is-independent-of-glun2-subunit-composition
#16
Jonathan M Wong, John A Gray
NMDA receptors (NMDARs) mediate both long-term potentiation (LTP) and long-term depression (LTD) and understanding how a single receptor can initiate both phenomena remains a major question in neuroscience. A prominent hypothesis implicates the NMDAR subunit composition, specifically GluN2A and GluN2B, in dictating the rules of synaptic plasticity. However, studies testing this hypothesis have yielded inconsistent and often contradictory results, especially for LTD. These inconsistent results may be due to challenges in the interpretation of subunit-selective pharmacology and in dissecting out the contributions of differential channel properties versus the interacting proteins unique to GluN2A or GluN2B...
March 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29581378/hipk2-mediated-transcriptional-control-of-nmda-receptor-subunit-expression-regulates-neuronal-survival-and-cell-death
#17
Yulei Shang, Jiasheng Zhang, Eric J Huang
NMDA receptors are critical for neuronal communication. Dysfunction in NMDA receptors has been implicated in neuropsychiatric diseases. While it is well recognized that the composition of NMDA receptors undergoes a GluN2B-to-GluN2A switch in early postnatal life, the mechanism regulating this switch remains unclear. Using transcriptomic and functional analyses in brain tissues from male and female Hipk2 +/+ and Hipk2 -/- mice, we showed that the HIPK2-JNK-c-Jun pathway is important in suppressing the transcription of Grin2a and Grin2c , which encodes the GluN2A and GluN2C subunits of the NMDA receptors, respectively...
April 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29578035/ras-inhibitor-s-trans-trans-farnesylthiosalicylic-acid-enhances-spatial-memory-and-hippocampal-long-term-potentiation-via-up-regulation-of-nmda-receptor
#18
Ya Wang, Tingting Chen, Zihao Yuan, Yajie Zhang, Baofeng Zhang, Liandong Zhao, Ling Chen
Statins by reducing farnesyl-pyrophosphate or farnesyl transferase inhibitors have been demonstrated to enhance spatial memory and long-term potentiation (LTP). The objective of this study was to investigate effects of the synthetic Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS) on spatial cognitive function in adult mice, synaptic plasticity in hippocampal CA1 regions, and NMDA receptor (NMDAr) activity of pyramidal cells. Here, we show that administering FTS (5 mg/kg, i.p.) enhanced spatial cognitive performance, as assessed via Morris water maze and Y-maze tests...
March 22, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29545389/mechanisms-of-critical-period-in-the-hippocampus-underlie-object-location-learning-and-memory-in-infant-rats
#19
Alessio Travaglia, Adam B Steinmetz, Janelle M Miranda, Cristina M Alberini
Episodic memories in early childhood are rapidly forgotten, a phenomenon that is associated with "infantile amnesia," the inability of adults to remember early-life experiences. We recently showed that early aversive contextual memory in infant rats, which is in fact rapidly forgotten, is actually not lost, as reminders presented later in life reinstate a long-lasting and context-specific memory. We also showed that the formation of this infantile memory recruits in the hippocampus mechanisms typical of developmental critical periods...
April 2018: Learning & Memory
https://www.readbyqxmd.com/read/29492616/intra-hippocampal-d-cycloserine-rescues-decreased-social-memory-spatial-learning-reversal-and-synaptophysin-levels-in-aged-rats
#20
Marta Portero-Tresserra, Margarita Martí-Nicolovius, Mireia Tarrés-Gatius, Ana Candalija, Gemma Guillazo-Blanch, Anna Vale-Martínez
RATIONALE: Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. OBJECTIVES AND METHODS: The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats...
May 2018: Psychopharmacology
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