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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
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/29079540/il-18-contributes-to-bone-cancer-pain-by-regulating-glia-cells-and-neuron-interaction
#4
Su Liu, Yue-Peng Liu, You Lv, Jun-Li Yao, Dong-Mei Yue, Mao-Yin Zhang, Dun-Yi Qi, Gong-Jian Liu
BACKGROUND: Glia cells hyperactivity has been proposed to be responsible for chronic pain, however, the mechanisms remain unclear. IL-18, released from glial cells, has been reported to be involved in neuropathic pain. Here, we investigated the role of IL-18 in bone cancer pain. METHODS: Bone cancer pain was mimicked by injecting Walker-256 mammary gland carcinoma cells into the intramedullary space of the tibia in rats. Expression and location of IL-18 and IL-18 receptor were tested...
October 24, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29073350/understanding-the-antibody-repertoire-in-neuropsychiatric-systemic-lupus-erythematosus-and-neuromyelitis-optica-spectrum-disorders-do-they-share-common-targets
#5
Simone Mader, Venkatesh Jeganathan, Yoshiyuki Arinuma, Yuichiro Fujieda, Irena Dujmovic, Jelena Drulovic, Yuka Shimizu, Yuko Sakuma, Joel N H Stern, Cynthia Aranow, Meggan Mackay, Shinsuke Yasuda, Tatsuya Atsumi, Shunsei Hirohata, Betty Diamond
OBJECTIVE: DWEYS-IgG cross-reactive with DNA and the N-methyl-D-aspartate receptor subunits GluN2A/GluN2B has been associated with neuropsychiatric systemic lupus erythematosus (NPSLE). DWEYS-IgG has not been investigated in demyelinating NPSLE (dNPSLE) or in another demyelinating disorder, Neuromyelitis Optica Spectrum Disorder (NMOSD), which is also a disease of young women and associated with aquaporin-4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibodies. We investigated the frequency of these brain-reactive antibodies in NPSLE, dNPSLE and NMOSD...
October 26, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29052618/a-role-for-prefrontal-cortical-nmda-receptors-in-murine-alcohol-heightened-aggression
#6
Emily L Newman, Miho Terunuma, Tiffany Wang, Nishani Hewage, Matthew B Bicakci, Stephen J Moss, Joseph F DeBold, Klaus A Miczek
Alcohol is associated with nearly half of all violent crimes committed in the United States; yet, a potential neural basis for this type of pathological aggression remains elusive. Alcohol may act on NMDA receptors (NMDARs) within cortical circuits to impede processing and to promote aggression. Here, male mice were characterized as alcohol-heightened (AHAs) or alcohol non-heightened aggressors (ANAs) during resident-intruder confrontations after self-administering 1.0 g/kg alcohol (6% w/v) or water. Alcohol produced a pathological-like pattern of aggression in AHAs; these mice shifted their bites to more vulnerable locations on the body of a submissive animal, including the anterior back and ventrum after consuming alcohol...
October 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29043770/a-novel-negative-allosteric-modulator-selective-for-glun2c-2d-containing-nmda-receptors-inhibits-synaptic-transmission-in-hippocampal-interneurons
#7
Sharon A Swanger, Katie M Vance, Timothy M Acker, Sommer S Zimmerman, John O DiRaddo, Scott J Myers, Christoffer Bundgaard, Cara A Mosley, Samantha L Summer, David S Menaldino, Henrik S Jensen, Dennis C Liotta, Stephen F Traynelis
N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 and two GluN2 subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional properties and gene expression patterns, which contribute to diverse functional roles for NMDARs in the brain. Here, we present a series of GluN2C/2D-selective negative allosteric modulators built around a N-aryl benzamide (NAB) core...
November 2, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29030575/adolescent-ethanol-exposure-enhances-nmda-receptor-mediated-currents-in-hippocampal-neurons-reversal-by-gabapentin
#8
H S Swartzwelder, Maeng-Hee Park, Shawn Acheson
Adolescent intermittent ethanol (AIE) exposure compromises neural function into adulthood. We have reported that astrocyte-secreted thrombospondins, and their target neuronal receptors (α2δ-1) are upregulated in the hippocampus in adulthood after AIE, suggesting aberrant excitatory synaptogenesis and hyperexcitability in memory-related circuits. Gabapentin antagonizes the interaction of thrombospondins (TSPs) with the α2δ-1 receptor, and thus may reverse or ameliorate the effects of AIE on hippocampal function...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030082/adx-47273-a-mglu5-receptor-positive-allosteric-modulator-attenuates-deficits-in-cognitive-flexibility-induced-by-withdrawal-from-binge-like-ethanol-exposure-in-rats
#9
Marta Marszalek-Grabska, Ewa Gibula-Bruzda, Anna Bodzon-Kulakowska, Piotr Suder, Kinga Gawel, Sylwia Talarek, Joanna Listos, Ewa Kedzierska, Wojciech Danysz, Jolanta H Kotlinska
Repeated exposure to and withdrawal from ethanol induces deficits in spatial reversal learning. Data indicate that metabotropic glutamate 5 (mGlu5) receptors are implicated in synaptic plasticity and learning and memory. These receptors functionally interact with N-methyl-d-aspartate (NMDA) receptors, and activation of one type results in the activation of the other. We examined whether (S)-(4-fluorophenyl)(3-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl (ADX-47273), a positive allosteric modulator (PAM) of mGlu5 receptor, attenuates deficits in reversal learning induced by withdrawal (11-13days) from 'binge-like' ethanol input (5...
October 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29024713/a-lack-of-glun2a-containing-nmda-receptors-confers-a-vulnerability-to-redox-dysregulation-consequences-on-parvalbumin-interneurons-and-their-perineuronal-nets
#10
Romain Cardis, Jan-Harry Cabungcal, Daniella Dwir, Kim Q Do, Pascal Steullet
The GluN2A subunit of NMDA receptors (NMDARs) plays a critical role during postnatal brain development as its expression increases while Glun2B expression decreases. Mutations and polymorphisms in GRIN2A gene, coding for GluN2A, are linked to developmental brain disorders such as mental retardation, epilepsy, schizophrenia. Published data suggest that GluN2A is involved in maturation and phenotypic maintenance of parvalbumin interneurons (PVIs), and these interneurons suffer from a deficient glutamatergic neurotransmission via GluN2A-containing NMDARs in schizophrenia...
October 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28993251/hypoxia-ischemia-modifies-postsynaptic-glun2b-containing-nmda-receptor-complexes-in-the-neonatal-mouse-brain
#11
Fuxin Lu, Guo Shao, Yongqiang Wang, Shenheng Guan, Alma L Burlingame, Xuemei Liu, Xiao Liang, Renatta Knox, Donna M Ferriero, Xiangning Jiang
The N-methyl-d-aspartate-type glutamate receptor (NMDAR)-associated multiprotein complexes are indispensable for synaptic plasticity and cognitive functions. While purification and proteomic analyses of these signaling complexes have been performed in adult rodent and human brain, much less is known about the protein composition of NMDAR complexes in the developing brain and their modifications by neonatal hypoxic-ischemic (HI) brain injury. In this study, the postsynaptic density proteins were prepared from postnatal day 9 naïve, sham-operated and HI-injured mouse cortex...
October 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28993142/ghrelin-upregulates-the-phosphorylation-of-the-glun2b-subunit-of-the-nmda-receptor-by-activating-ghsr1a-and-fyn-in-the-rat-hippocampus
#12
Liza Berrout, Masako Isokawa
Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity...
October 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28986874/design-of-light-sensitive-nmdars-by-genetically-encoded-photo-cross-linkers
#13
Meilin Tian, Shixin Ye
Genetic code expansion exploiting unnatural amino acids (Uaas) is a powerful technique to create novel protein function in vivo. Here, we provide a protocol for the incorporation of two UV-sensitive crosslinking Uaas into NMDA receptors (NMDARs), a type of glutamate-gated ion channels mediating fast synaptic transmission. Through heterologous expression in Xenopus laevis oocytes, we have identified light-sensitive NMDARs of GluN2B subtype by using the two-electrode voltage electrophysiology measurement in combination with online-UV application...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986873/glun2b-subunit-labeling-with-fluorescent-probes-and-high-resolution-live-imaging
#14
Cécile Perrio, Olivier Nicole, Alain Buisson
Laser Scanning Confocal Microscopy (LSCM) imaging using an appropriate fluorescent probe enables the visualization of a molecular target with high resolution, and represents a method of choice for studying expression, subcellular location, and trafficking of receptors in living cells. The chemical, physical, and pharmacological properties of the probe remain essential. Here, we describe (1) the preparation of a specific probe for NMDAR GluN2B receptor by conjugation of fluorescein to an ifenprodil-based ligand, (2) an in vitro functional assay by calcium imaging for GluN2B binding and inhibition evaluation of the probe, and (3) the labeling and confocal imaging of GluN2B in DS-red labeled living cortical neurons...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28981594/neuron-targeted-caveolin-1-promotes-ultrastructural-and-functional-hippocampal-synaptic-plasticity
#15
Junji Egawa, Alice Zemljic-Harpf, Chitra D Mandyam, Ingrid R Niesman, Larisa V Lysenko, Alexander M Kleschevnikov, David M Roth, Hemal H Patel, Piyush M Patel, Brian P Head
A delicate interneuronal communication between pre- and postsynaptic membranes is critical for synaptic plasticity and the formation of memory. Evidence shows that membrane/lipid rafts (MLRs), plasma membrane microdomains enriched in cholesterol and sphingolipids, organize presynaptic proteins and postsynaptic receptors necessary for synaptic formation and signaling. MLRs establish a cell polarity that facilitates transduction of extracellular cues to the intracellular environment. Here we show that neuron-targeted overexpression of an MLR protein, caveolin-1 (SynCav1), in the adult mouse hippocampus increased the number of presynaptic vesicles per bouton, total excitatory type I glutamatergic synapses, number of same-dendrite multiple-synapse boutons, increased myelination, increased long-term potentiation, and increased MLR-localized N-methyl-d-aspartate receptor subunits (GluN1, GluN2A, and GluN2B)...
July 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28973019/beta-arrestin-1-regulation-of-reward-motivated-behaviors-and-glutamatergic-function
#16
Nitish Mittal, Ani Minasyan, Nicole Romaneschi, Joshua K Hakimian, Gabriel Gonzalez-Fernandez, Ralph Albert, Nina Desai, Ian A Mendez, Timothy Schallert, Sean B Ostlund, Wendy Walwyn
The two highly homologous non-visual arrestins, beta-arrestin 1 and 2, are ubiquitously expressed in the central nervous system, yet knowledge of their disparate roles is limited. While beta-arrestin 2 (βarr2) has been implicated in several aspects of reward-related learning and behavior, very little is known about the behavioral function of beta-arrestin 1 (βarr1). Using mice lacking βarr1, we focused on the role of this scaffolding and signal transduction protein in reward-motivated behaviors and in striatal glutamatergic function...
2017: PloS One
https://www.readbyqxmd.com/read/28972129/camkii-regulates-synaptic-nmda-receptor-activity-of-hypothalamic-presympathetic-neurons-and-sympathetic-outflow-in-hypertension
#17
De-Pei Li, Jing-Jing Zhou, Jixiang Zhang, Hui-Lin Pan
NMDAR activity in the hypothalamic paraventricular nucleus (PVN) is increased and critically involved in heightened sympathetic vasomotor tone in hypertension. Calcium/calmodulin-dependent protein kinase II (CaMKII) binds to and modulates NMDAR activity. In this study, we determined the role of CaMKII in regulating NMDAR activity of PVN presympathetic neurons in male spontaneously hypertensive rats (SHRs). NMDAR-mediated EPSCs and puff NMDA-elicited currents were recorded in spinally projecting PVN neurons in SHRs and male Wistar-Kyoto (WKY) rats...
November 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28969472/-express-propofol-produces-preventive-analgesia-via-glun2b-containing-nmda-receptor-erk1-2-signaling-pathway-in-a-rat-model-of-inflammatory-pain
#18
Qiu Qiu, Liting Sun, Xiao-Min Wang, Amy C Y Lo, Kar Lok Wong, Pan Gu, Sau Ching Stanley Wong, Chi Wai Cheung
No abstract text is available yet for this article.
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28957809/geniposide-attenuates-post-ischaemic-neurovascular-damage-via-glun2a-akt-erk-dependent-mechanism
#19
Baosheng Huang, Panhong Chen, Lei Huang, Shuai Li, Ronglan Zhu, Tao Sheng, Wan Yu, Zheng Chen, Tianlu Wang
BACKGROUND/AIMS: Calcium-permeable ionotropic NMDAR-mediated hyperactivity is regarded as the critical factor in modulating the development of ischaemic stroke. Recently, there has been increasing interest in preventing post-stroke neuronal death by focusing on intervening in the function of subpopulations of NMDARs and their downstream signalling. Geniposide, an iridoid glycoside, has been found to have cytoprotective functions in various conditions. However, it is still unclear whether and how geniposide affects neuronal insult under experimental stroke...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28954811/preclinical-characterization-of-r-3-3s-4s-3-fluoro-4-4-hydroxyphenyl-piperidin-1-yl-1-4-methylbenzyl-pyrrolidin-2-one-bms-986169-a-novel-intravenous-glutamate-n-methyl-d-aspartate-2b-glun2b-receptor-negative-allosteric-modulator-with-potential-in-major-depressive
#20
Linda J Bristow, Jyoti Gulia, Michael R Weed, Bettadapura N Srikumar, Yu-Wen Li, John D Graef, Pattipati S Naidu, Charulatha Sanmathi, Jayant Aher, Tanmaya Bastia, Mahesh Paschapur, Narasimharaju Kalidindi, Kuchibholta Vijaya Kumar, Thaddeus Molski, Rick Pieschl, Alda Fernandes, Jeffrey M Brown, Digavalli V Sivarao, Kimberly Newberry, Mark Bookbinder, Joseph Polino, Deborah Keavy, Amy Newton, Eric Shields, Jean Simmermacher, James Kempson, Jianqing Li, Huiping Zhang, Arvind Mathur, Raja Reddy Kallem, Meenakshee Sinha, Manjunath Ramarao, Reeba K Vikramadithyan, Srinivasan Thangathirupathy, Jayakumar Warrier, Joanne J Bronson, Richard E Olson, John E Macor, Charlie F Albright, Dalton King, Lorin A Thompson, Lawrence R Marcin, Michael Sinz
(R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (BMS-986169), and the phosphate prodrug (BMS-986163), were identified from a drug discovery effort focused on the development of novel, intravenous, glutamate N-methyl-D-aspartate 2B receptor (GluN2B) negative allosteric modulators for treatment resistant depression (TRD). BMS-986169 showed high binding affinity for the GluN2B subunit allosteric modulatory site (Ki = 4.03-6.3 nM) and selectively inhibited GluN2B receptor function in Xenopus oocytes expressing human N-methyl-D-aspartate receptor subtypes (IC50 = 24...
September 27, 2017: Journal of Pharmacology and Experimental Therapeutics
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