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Glutamate receptors

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https://www.readbyqxmd.com/read/28098344/inhibition-of-oxytocin-and-vasopressin-neuron-activity-in-rat-hypothalamic-paraventricular-nucleus-by-relaxin-3-rxfp3-signalling
#1
Alan Kania, Anna Czerw, Agnieszka Grabowiecka, Camila de Ávila, Tomasz Blasiak, Zenon Rajfur, Marian H Lewandowski, Grzegorz Hess, Elena Timofeeva, Andrew L Gundlach, Anna Blasiak
KEY-POINTS: Relaxin-3 is a stress-responsive neuropeptide that acts at its cognate receptor, RXFP3, to alter behaviours including feeding. In this study, we have demonstrated a direct, RXFP3-dependent, inhibitory action of relaxin-3 on oxytocin and vasopressin PVN neuron electrical activity, a putative cellular mechanism of orexinergic actions of relaxin-3. We observed a Gαi/o -protein-dependent inhibitory influence of selective RXFP3 activation on PVN neuronal activity in vitro and demonstrated a direct action of RXFP3 activation on oxytocin and vasopressin PVN neurons, confirmed by their abundant expression of RXFP3 mRNA...
January 18, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28098256/dopamine-promotes-nmda-receptor-hypofunction-in-the-retina-through-d1-receptor-mediated-csk-activation-src-inhibition-and-decrease-of-glun2b-phosphorylation
#2
Renato Socodato, Felipe N Santiago, Camila C Portugal, Ivan Domith, Thaísa G Encarnação, Erick C Loiola, Ana L M Ventura, Marcelo Cossenza, João B Relvas, Newton G Castro, Roberto Paes-de-Carvalho
Dopamine and glutamate are critical neurotransmitters involved in light-induced synaptic activity in the retina. In brain neurons, dopamine D1 receptors (D1Rs) and the cytosolic protein tyrosine kinase Src can, independently, modulate the behavior of NMDA-type glutamate receptors (NMDARs). Here we studied the interplay between D1Rs, Src and NMDARs in retinal neurons. We reveal that dopamine-mediated D1R stimulation provoked NMDAR hypofunction in retinal neurons by attenuating NMDA-gated currents, by preventing NMDA-elicited calcium mobilization and by decreasing the phosphorylation of NMDAR subunit GluN2B...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097463/neurokinin-1-receptor-immunopositive-neurons-in-the-medullary-dorsal-horn-provide-collateral-axons-to-both-the-thalamus-and-parabrachial-nucleus-in-rats
#3
Xu Li, Shun-Nan Ge, Yang Li, Han-Tao Wang
It has been suggested that the trigemino-thalamic and trigemino-parabrachial projection neurons in the medullary dorsal horn (MDH) are highly implicated in the sensory-discriminative and emotional/affective aspects of orofacial pain, respectively. In previous studies, some neurons were reported to send projections to both the thalamus and parabrachial nucleus by way of collaterals in the MDH. However, little is known about the chemoarchitecture of this group of neurons. Thus, in the present study, we determined whether the neurokinin-1 (NK-1) receptor, which is crucial for primary orofacial pain signaling, was expressed in MDH neurons co-innervating the thalamus and parabrachial nucleus...
January 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28097219/key-role-of-the-dopamine-d4-receptor-in-the-modulation-of-corticostriatal-glutamatergic-neurotransmission
#4
Jordi Bonaventura, César Quiroz, Ning-Sheng Cai, Marcelo Rubinstein, Gianluigi Tanda, Sergi Ferré
Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D4 receptor with the long intracellular domain of a human DRD4 polymorphic variant associated with attention deficit hyperactivity disorder (ADHD)...
January 2017: Science Advances
https://www.readbyqxmd.com/read/28096465/sequences-within-the-c-terminus-of-the-metabotropic-glutamate-receptor-mglur5-are-responsible-for-inner-nuclear-membrane-localization
#5
Ismail Sergin, Yuh-Jiin I Jong, Steven K Harmon, Vikas Kumar, Karen L O'Malley
Traditionally G-protein coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5, mGluR5, is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096462/unique-contributions-of-an-arginine-side-chain-to-ligand-recognition-in-a-glutamate-gated-chloride-channel
#6
Timothy Lynagh, Vitaly V Komnatnyy, Stephan A Pless
Glutamate recognition by neurotransmitter receptors often relies on arginine (Arg) residues in the binding site, leading to the assumption that charge-charge interactions underlie ligand recognition. However, assessing the precise chemical contribution of Arg side chains to protein function and pharmacology has proven to be exceedingly difficult in such large and complex proteins. Using the in vivo nonsense suppression approach, we report the first successful incorporation of the isosteric, titratable Arg analog, canavanine, into a neurotransmitter receptor in a living cell, utilizing a glutamate-gated chloride channel from the nematode Haemonchus contortus...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28095420/molecular-mechanism-of-disease-associated-mutations-in-the-pre-m1-helix-of-nmda-receptors-and-potential-rescue-pharmacology
#7
Kevin K Ogden, Wenjuan Chen, Sharon A Swanger, Miranda J McDaniel, Linlin Z Fan, Chun Hu, Anel Tankovic, Hirofumi Kusumoto, Gabrielle J Kosobucki, Anthony J Schulien, Zhuocheng Su, Joseph Pecha, Subhrajit Bhattacharya, Slavé Petrovski, Adam E Cohen, Elias Aizenman, Stephen F Traynelis, Hongjie Yuan
N-methyl-D-aspartate receptors (NMDARs), ligand-gated ionotropic glutamate receptors, play key roles in normal brain development and various neurological disorders. Here we use standing variation data from the human population to assess which protein domains within NMDAR GluN1, GluN2A and GluN2B subunits show the strongest signal for being depleted of missense variants. We find that this includes the GluN2 pre-M1 helix and linker between the agonist-binding domain (ABD) and first transmembrane domain (M1). We then evaluate the functional changes of multiple missense mutations in the NMDAR pre-M1 helix found in children with epilepsy and developmental delay...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28093554/tumour-necrosis-factor-mediated-homeostatic-synaptic-plasticity-in-behavioural-models-testing-a-role-in-maternal-immune-activation
#8
Sarah C Konefal, David Stellwagen
The proinflammatory cytokine tumour necrosis factor-alpha (TNFα) has long been characterized for its role in the innate immune system, but more recently has been found to have a distinct role in the nervous system that does not overlap with other proinflammatory cytokines. Through regulation of neuronal glutamate and GABA receptor trafficking, TNF mediates a homeostatic form of synaptic plasticity, but plays no direct role in Hebbian forms of plasticity. As yet, there is no evidence to suggest that this adaptive plasticity plays a significant role in normal development, but it does maintain neuronal circuit function in the face of several types of disruption...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28092865/investigations-on-the-immunosuppressive-activity-of-derivatives-of-mycophenolic-acid-in-immature-dendritic-cells
#9
Dorota Iwaszkiewicz-Grzes, Grzegorz Cholewinski, Agata Kot-Wasik, Piotr Trzonkowski, Krystyna Dzierzbicka
The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors...
January 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28092020/early-life-social-isolation-induced-depressive-like-behavior-in-rats-results-in-microglial-activation-and-neuronal-histone-methylation-that-are-mitigated-by-minocycline
#10
Hong-Tao Wang, Fu-Lian Huang, Zhao-Lan Hu, Wen-Juan Zhang, Xiao-Qing Qiao, Yan-Qing Huang, Ru-Ping Dai, Fang Li, Chang-Qi Li
Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microglia, levels of histone methylation, as well as expression of glutamate receptor subunits in the hippocampus. We found that depressive-like behavior was induced after ESI as determined by sucrose preference and forced swimming tests...
January 16, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28089597/magnesium-and-calcium-ions-differentially-affect-human-serine-racemase-activity-and-modulate-its-quaternary-equilibrium-toward-a-tetrameric-form
#11
Stefano Bruno, Marilena Margiotta, Francesco Marchesani, Gianluca Paredi, Valentina Orlandi, Serena Faggiano, Luca Ronda, Barbara Campanini, Andrea Mozzarelli
Serine racemase is the pyridoxal 5'-phosphate dependent enzyme that catalyzes both production and catabolism of d-serine, a co-agonist of the NMDA glutamate receptors. Mg(2+), or, alternatively, Ca(2+), activate human serine racemase by binding both at a specific site and - as ATP-metal complexes - at a distinct ATP binding site. We show that Mg(2+) and Ca(2+) bind at the metal binding site with a 4.5-fold difference in affinity, producing a similar thermal stabilization and partially shifting the dimer-tetramer equilibrium in favour of the latter...
January 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088471/effects-of-group-i-metabotropic-glutamate-receptor-antagonists-on-sensitivity-to-reinforcer-magnitude-and-delayed-reinforcement-in-a-delay-discounting-task-in-rats-contribution-of-delay-presentation-order
#12
Justin R Yates, Katherine K Rogers, Benjamin T Gunkel, Nicholas A Prior, Mallory N Hughes, Sara M Sharpe, Hunter L Campbell, Anthony B Johnson, Margaret G Keller, Kerry A Breitenstein, Hansen N Shults
Metabotropic glutamate receptor 1 (mGluR1) blockade has been shown to decrease impulsive choice, as measured in delay discounting. However, several variables are known to influence an animal's discounting, including sensitivity to delayed reinforcement and sensitivity to reinforcer magnitude. The goal of this experiment was to determine the effects of mGluR1, as well as mGluR5, antagonism on these parameters. Forty Sprague Dawley rats were trained in delay discounting, in which consistently choosing a small, immediate reward reflects impulsive choice...
January 11, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28088112/a-current-perspective-on-the-oncopreventive-and-oncolytic-properties-of-selective-serotonin-reuptake-inhibitors
#13
REVIEW
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28087766/control-of-amygdala-circuits-by-5-ht-neurons-via-5-ht-and-glutamate-co-transmission
#14
Ayesha Sengupta, Marco Bocchio, David M Bannerman, Trevor Sharp, Marco Capogna
: The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Thus, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin (ChR2) genetically targeted to 5-HT neurons...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28087150/apelin-protects-against-nmda-induced-retinal-neuronal-death-via-an-apj-receptor-by-activating-akt-and-erk1-2-and-suppressing-tnf-%C3%AE-expression-in-mice
#15
Yuki Ishimaru, Akihide Sumino, Daiki Kajioka, Fumiya Shibagaki, Akiko Yamamuro, Yasuhiro Yoshioka, Sadaaki Maeda
Glutamate excitotoxicity mediated by N-methyl-d-aspartate (NMDA) receptors is an important cause of retinal ganglion cell death in glaucoma. To elucidate whether apelin protects against retinal neuronal cell death, we examined protective effects of exogenous and endogenous apelin on neuronal cell death induced by intravitreal injection of NMDA in the retinas of mice. An intravitreal injection of NMDA induced neuronal cell death in both the retinal ganglion cell layer and inner nuclear layer, and reduced the amplitudes of scotopic threshold response (STR) in electroretinography studies...
December 24, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28077715/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#16
Amber L Alhadeff, Ruby A Holland, Huiyuan Zheng, Linda Rinaman, Harvey J Grill, Bart C De Jonghe
: Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN) and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We demonstrated previously that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we used neuroanatomical tracing, immunofluorescence, and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections coexpress vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077487/calcium-permeable-ampa-receptors-and-silent%C3%A2-synapses-in-cocaine-conditioned-place-preference
#17
Avani Shukla, Anna Beroun, Myrto Panopoulou, Peter A Neumann, Seth Gn Grant, M Foster Olive, Yan Dong, Oliver M Schlüter
Exposure to cocaine generates silent synapses in the nucleus accumbens (NAc), whose eventual unsilencing/maturation by recruitment of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) after drug withdrawal results in profound remodeling of NAc neuro-circuits. Silent synapse-based NAc remodeling was shown to be critical for several drug-induced behaviors, but its role in acquisition and retention of the association between drug rewarding effects and drug-associated contexts has remained unclear. Here, we find that the postsynaptic proteins PSD-93, PSD-95, and SAP102 differentially regulate excitatory synapse properties in the NAc...
January 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28077092/phylogenetic-analysis-of-ionotropic-l-glutamate-receptor-genes-in-the-bilateria-with-special-notes-on-aplysia-californica
#18
Justin B Greer, Sawsan Khuri, Lynne A Fieber
BACKGROUND: The neurotransmitter L-Glutamate (L-Glu) acting at ionotropic L-Glu receptors (iGluR) conveys fast excitatory signal transmission in the nervous systems of all animals. iGluR-dependent neurotransmission is a key component of the synaptic plasticity that underlies learning and memory. During learning, two subtypes of iGluR, α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and N-methyl-D-aspartate receptors (NMDAR), are dynamically regulated postsynaptically in vertebrates...
January 11, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28074469/development-of-cone-photoreceptors-and-their-synapses-in-the-human-and-monkey-fovea
#19
Anita Hendrickson, Chi Zhang
During retinal development, ribbon synapse assembly in the photoreceptors is a crucial step involving numerous molecules. While the developmental sequence of plexiform layers in human retina has been characterized, the molecular steps of synaptogenesis remain largely unknown. In the present study, we focused on the central rod-free region of primate retina, the fovea, to specifically investigate the development of cone photoreceptor ribbon synapses. Immunocytochemistry and electron microscopy were utilized to track the expression of photoreceptor transduction proteins and ribbon and synaptic markers in fetal human and Macaca retina...
January 11, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28074037/developmental-pruning-of-excitatory-synaptic-inputs-to-parvalbumin-interneurons-in-monkey-prefrontal-cortex
#20
Daniel W Chung, Zachary P Wills, Kenneth N Fish, David A Lewis
Working memory requires efficient excitatory drive to parvalbumin-positive (PV) interneurons in the primate dorsolateral prefrontal cortex (DLPFC). Developmental pruning eliminates superfluous excitatory inputs, suggesting that working memory maturation during adolescence requires pruning of excitatory inputs to PV interneurons. Therefore, we tested the hypothesis that excitatory synapses on PV interneurons are pruned during adolescence. The density of excitatory synapses, defined by overlapping vesicular glutamate transporter 1-positive (VGlut1+) and postsynaptic density 95-positive (PSD95+) puncta, on PV interneurons was lower in postpubertal relative to prepubertal monkeys...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
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