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Ampa receptors

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https://www.readbyqxmd.com/read/28636281/aryl-and-heteroaryl-substituted-phenylalanines-as-ampa-receptor-ligands
#1
Ewa Szymańska, Paulina Chałupnik, Tommy N Johansen, Birgitte Nielsen, Ana Maria Cuñado Moral, Darryl S Pickering, Anna Więckowska, Katarzyna Kieć-Kononowicz
A series of racemic unnatural amino acids was rationally designed on the basis of recently published X-ray structures of the GluA2 LBD with bound phenylalanine-based antagonists. Twelve new diaryl- or aryl/heteroaryl-substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3'-hydroxy-5-(1H-pyrazol-4-yl)-[1,1'-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28630296/subunit-specific-role-for-the-amino-terminal-domain-of-ampa-receptors-in-synaptic-targeting
#2
Javier Díaz-Alonso, Yujiao J Sun, Adam J Granger, Jonathan M Levy, Sabine M Blankenship, Roger A Nicoll
The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD of GluA1 is absent fail to translocate, establishing a critical role of the ATD of GluA1. Inserting GFP into the ATD interferes with the constitutive synaptic trafficking of GluA1, but not GluA2, mimicking the deletion of the ATD...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28628388/coordination-of-ampa-receptor-trafficking-by-rab-small-gtpases
#3
Angelika Hausser, Katalin Schlett
Synaptic connections in the brain are continuously weakened or strengthened in response to changes in neuronal activity. This process, known as synaptic plasticity, is the cellular basis for learning and memory, and is thought to be altered in several neuronal disorders. An important aspect of synaptic plasticity is the tightly controlled trafficking and synaptic targeting of the AMPA-type glutamate receptors, which are the major mediators of fast excitatory transmission in the brain. This review addresses the role of Rab GTPases in AMPA receptor trafficking in neurons under basal conditions and during activity-induced synaptic plasticity, especially during long-term potentiation (LTP) and long-term depression (LTD)...
June 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28624414/corneal-kindled-c57bl-6-mice-exhibit-saturated-dentate-gyrus-long-term-potentiation-and-associated-memory-deficits-in-the-absence-of-overt-neuron-loss
#4
Gregory J Remigio, Jaycie L Loewen, Sage Heuston, Colin Helgeson, H Steve White, Karen S Wilcox, Peter J West
Memory deficits have a significant impact on the quality of life of patients with epilepsy and currently no effective treatments exist to mitigate this comorbidity. While these cognitive comorbidities can be associated with varying degrees of hippocampal cell death and hippocampal sclerosis, more subtle changes in hippocampal physiology independent of cell loss may underlie memory dysfunction in many epilepsy patients. Accordingly, animal models of epilepsy or epileptic processes exhibiting memory deficits in the absence of cell loss could facilitate novel therapy discovery...
June 15, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28624183/the-neuroprotective-effect-of-perampanel-in-lithium-pilocarpine-rat-seizure-model
#5
Ting Wu, Katsutoshi Ido, Yoshihide Osada, Sadaharu Kotani, Akira Tamaoka, Takahisa Hanada
PURPOSE: Status epilepticus (SE) causes irreversible neurodegeneration if not terminated quickly. Perampanel (PER), a potent AMPA receptor antagonist, has previously been shown to terminate seizures in the lithium-pilocarpine SE model. In the present study, we assessed whether PER would also prevent neuronal damage in this model. METHODS: SE was induced in rats using lithium chloride and pilocarpine. Initiation of SE was defined as continuous seizures that exhibited as rearing accompanied by bilateral forelimb clonus (Racine score 4)...
June 14, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28621434/eea1-restores-homeostatic-synaptic-plasticity-in-hippocampal-neurons-from-rett-syndrome-mice
#6
Xin Xu, Lucas Pozzo-Miller
Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in MECP2, the gene encoding the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). Deletion of Mecp2 in mice results in an imbalance of synaptic excitation and inhibition in hippocampal pyramidal neurons, which affects "Hebbian" long-term synaptic plasticity. Since the excitatory/inhibitory (E/I) balance is maintained by homeostatic mechanisms, we examined the role of MeCP2 in homeostatic synaptic plasticity (HSP) at excitatory synapses...
June 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28620737/analysis-of-bmaa-enantiomers-in-cycads-cyanobacteria-and-mammals-in-vivo-formation-and-toxicity-of-d-bmaa
#7
J S Metcalf, Doug Lobner, Sandra Anne Banack, Gregory A Cox, Peter B Nunn, Peter B Wyatt, Paul Alan Cox
Chronic dietary exposure to the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA) triggers neuropathology in non-human primates, providing support for the theory that BMAA causes a fatal neurodegenerative illness among the indigenous Chamorro people of Guam. However, since there are two stereoisomers of BMAA, it is important to know if both can occur in nature, and if so, what role they might play in disease causation. As a first step, we analysed both BMAA enantiomers in cyanobacteria, cycads, and in mammals orally dosed with L-BMAA, to determine if enantiomeric changes could occur in vivo...
June 15, 2017: Amino Acids
https://www.readbyqxmd.com/read/28611594/overexpression-of-mineralocorticoid-receptors-in-the-mouse-forebrain-partly-alleviates-the-effects-of-chronic-early-life-stress-on-spatial-memory-neurogenesis-and-synaptic-function-in-the-dentate-gyrus
#8
Sofia Kanatsou, Henk Karst, Despoina Kortesidou, Rachelle A van den Akker, Jan den Blaauwen, Anjanette P Harris, Jonathan R Seckl, Harm J Krugers, Marian Joels
Evidence from human studies suggests that high expression of brain mineralocorticoid receptors (MR) may promote resilience against negative consequences of stress exposure, including childhood trauma. We examined, in mice, whether brain MR overexpression can alleviate the effects of chronic early life stress (ELS) on contextual memory formation under low and high stress conditions, and neurogenesis and synaptic function of dentate gyrus granular cells. Male mice were exposed to ELS by housing the dam with limited nesting and bedding material from postnatal day (PND) 2 to 9...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28609610/an-rna-aptamer-capable-of-forming-hydrogel-by-self-assembly
#9
Zhen Huang, Gagan N Kangovi, Wei Wen, Sangwoo Lee, Li Niu
Hydrogels are supramolecular assemblies with both solute transport properties like liquids and mechanical properties like elastomers. To date, every type of biomolecules, except ribonucleic acid (RNA), are capable of forming hydrogel. Here we report an RNA that forms hydrogel by self-assembly. This RNA is originally identified by systematic evolution of ligands by exponential enrichment (SELEX) to enhance the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors as a potential RNA drug for treatment of cognitive disorders...
June 13, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28608780/signalling-through-ampa-receptors-on-oligodendrocyte-precursors-promotes-myelination-by-enhancing-oligodendrocyte-survival
#10
Eleni Kougioumtzidou, Takahiro Shimizu, Nicola B Hamilton, Koujiro Tohyama, Rolf Sprengel, Hannah Monyer, David Attwell, William D Richardson
Myelin, made by oligodendrocytes, is essential for rapid information transfer in the central nervous system. Oligodendrocyte precursors (OPs) receive glutamatergic synaptic input from axons but how this affects their development is unclear. Murine OPs in white matter express AMPA receptor (AMPAR) subunits GluA2, GluA3 and GluA4. We generated mice in which OPs lack both GluA2 and GluA3, or all three subunits GluA2/3/4, which respectively reduced or abolished AMPAR-mediated input to OPs. In both double- and triple-knockouts OP proliferation and number were unchanged but ~25% fewer oligodendrocytes survived in the subcortical white matter during development...
June 13, 2017: ELife
https://www.readbyqxmd.com/read/28606856/antinociceptive-effect-of-botulinum-toxin-a-involves-alterations-in-ampa-receptor-expression-and-glutamate-release-in-spinal-dorsal-horn-neurons
#11
Bin Hong, LingLing Yao, Linhui Ni, Li Wang, XingYue Hu
The use of botulinum toxin A (BTX-A) for various clinical therapeutic applications is increasing. It is widely believed that peripheral therapeutic or toxic effects of BTX-A are exclusively mediated by SNAP-25 cleavage. There is growing evidence of long-distance retrograde axonal transport of BTX-A on entering the central nervous system, subsequent to a local injection of the toxin. However, the prevalence of central antinociceptive effects after BTX-A peripheral application and its underlying mechanisms are unclear...
June 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28603025/the-ampa-receptor-positive-allosteric-modulator-s-47445-rescues-in%C3%A2-vivo-ca3-ca1-long-term-potentiation-and-structural-synaptic-changes-in-old-mice
#12
Albert Giralt, María Ángeles Gómez-Climent, Rafael Alcalá, Sylvie Bretin, Daniel Bertrand, José María Delgado-García, Esther Pérez-Navarro, Jordi Alberch, Agnès Gruart
Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are small molecules that decrease deactivation of AMPARs via an allosteric site. These molecules keep the receptor in an active state. Interestingly, this type of modulator has been proposed for treating cognitive decline in ageing, dementias, and Alzheimer's disease (AD). S 47445 (8-cyclopropyl-3-[2-(3-fluorophenyl)ethyl]-7,8-dihydro-3H-[1,3]oxazino[6,5-g][1,2,3]benzotriazine-4,9-dione) is a novel AMPAR positive allosteric modulator (AMPA-PAM)...
June 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28594440/calcium-signalling-in-medial-intercalated-cell-dendrites-and-spines
#13
Cornelia Strobel, Robert K P Sullivan, Peter Stratton, Pankaj Sah
The amygdala plays a central role in fear conditioning and extinction. The medial intercalated (mITC) neurons are GABAergic cell clusters interspaced between the basolateral (BLA) and central amygdala (CeA). These neurons are thought to play a key role in fear and extinction, controlling the output of the CeA by feed-forward inhibition. BLA to mITC cell inputs are though to undergo synaptic plasticity, a mechanism underlying learning, which is mediated by NMDA-receptor dependent mechanisms that require changes in cytosolic calcium...
June 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28591602/configurational-preference-of-the-glutamate-receptor-ligand-binding-domain-dimers
#14
Michael Yonkunas, Maiti Buddhadev, Jose C Flores Canales, Maria G Kurnikova
Ionotropic glutamate receptors are a family of tetrameric ion channels with functional states consisting of nonconducting, conducting, and desensitized states that are starting to become well characterized by electrophysiological and biophysical studies. However, the structure and relative energetics of these states beyond the general structure of the receptor are still not well understood. It is known that the interface between monomeric subunits of the tetramer plays a major role in distinguishing these functional states...
June 6, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28589422/modulatory-function-of-nmda-glutamate-receptor-on-mc3-mc4-receptors-agonist-induced-hypophagia-in-neonatal-meat-type-chicken
#15
Fariba Ahmadi, Morteza Zendehdel, Vahab Babapour, Negar Panahi, Shahin Hassanpour, Mina Khodadadi
Melanocortin 3 and 4 receptors (MC3R and MC4R) are known as the main receptors for melanocortin-induced hypophagia in mammalian and poultry. Also, central glutamatergic system has mediatory role on function of the melanocortin system in some brain areas. So, the aim of the current study was to determine the role of MC3/MC4 receptors agonist on food intake and its interaction with glutamatergic in 3-h food-deprived (FD3) neonatal broilers. In experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, MTII (MC3/MC4 receptors agonist; 2...
June 6, 2017: Veterinary Research Communications
https://www.readbyqxmd.com/read/28585865/protein-kinase-c-epsilon-delays-latency-until-anoxic-depolarization-through-arc-expression-and-glur2-internalization
#16
Charles H Cohan, Holly M Stradecki-Cohan, Kahlilia C Morris-Blanco, Nathalie Khoury, Kevin B Koronowski, Mehdi Youbi, Clinton B Wright, Miguel A Perez-Pinzon
Global cerebral ischemia is a debilitating injury that damages the CA1 region of the hippocampus, an area important for learning and memory. Protein kinase C epsilon (PKCɛ) activation is a critical component of many neuroprotective treatments. The ability of PKCɛ activation to regulate AMPA receptors (AMPARs) remains unexplored despite the role of AMPARs in excitotoxicity after brain ischemia. We determined that PKCɛ activation increased expression of a protein linked to learning and memory, activity-regulated cytoskeleton-associated protein (arc)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28585190/spinal-ampa-receptor-glua1-ser831-phosphorylation-controls-chronic-alcohol-consumption-produced-prolongation-of-postsurgical-pain
#17
Sufang Liu, Zhiying Zhao, Yan Guo, Hui Shu, Changsheng Li, Yuanyuan Tang, Ying Xing, Feng Tao
Previous studies have shown that excessive alcohol drinking is associated with chronic pain development; however, the molecular mechanism underlying this association is poorly understood. In this study, we investigated the effect of chronic alcohol consumption on plantar incision-induced postsurgical pain. We observed that 4-week ethanol drinking significantly prolonged plantar incision-induced mechanical pain, but not thermal pain. The chronic alcohol consumption enhanced plantar incision-produced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 phosphorylation at the Ser831 site in the spinal cord...
June 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28582391/all-atom-nmda-receptor-transmembrane-domain-model-development-and-simulations-in-lipid-bilayers-and-water
#18
Samaneh Mesbahi-Vasey, Lea Veras, Michael Yonkunas, Jon W Johnson, Maria G Kurnikova
N-methyl-d-aspartate receptors (NMDARs) are members of the ionotropic glutamate receptor family that mediate excitatory synaptic transmission in the central nervous system. The channels of NMDARs are permeable to Ca2+ but blocked by Mg2+, distinctive properties that underlie essential brain processes such as induction of synaptic plasticity. However, due to limited structural information about the NMDAR transmembrane ion channel forming domain, the mechanism of divalent cation permeation and block is understood poorly...
2017: PloS One
https://www.readbyqxmd.com/read/28580416/glua2-lacking-ampa-receptors-and-nitric-oxide-signaling-gate-spike-timing-dependent-potentiation-of-glutamate-synapses-in-the-dorsal-raphe-nucleus
#19
Samir Haj-Dahmane, Jean Claude Béïque, Roh-Yu Shen
The dorsal raphe nucleus (DRn) receives glutamatergic inputs from numerous brain areas that control the function of DRn serotonin (5-HT) neurons. By integrating these synaptic inputs, 5-HT neurons modulate a plethora of behaviors and physiological functions. However, it remains unknown whether the excitatory inputs onto DRn 5-HT neurons can undergo activity-dependent change of strength, as well as the mechanisms that control their plasticity. Here, we describe a novel form of spike-timing-dependent long-term potentiation (tLTP) of glutamate synapses onto rat DRn 5-HT neurons...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28578480/acute-neuroinflammation-promotes-cell-responses-to-1800%C3%A2-mhz-gsm-electromagnetic-fields-in-the-rat-cerebral-cortex
#20
Julie Lameth, Annie Gervais, Catherine Colin, Philippe Lévêque, Thérèse M Jay, Jean-Marc Edeline, Michel Mallat
Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2...
June 3, 2017: Neurotoxicity Research
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