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https://www.readbyqxmd.com/read/28733972/expression-and-function-of-the-metabotropic-purinergic-p2y-receptor-family-in-experimental-seizure-models-and-patients-with-drug-refractory-epilepsy
#1
Mariana Alves, Rosa Gomez-Villafuertes, Norman Delanty, Michael A Farrell, Donncha F O'Brien, Maria Teresa Miras-Portugal, Miguel Diaz Hernandez, David C Henshall, Tobias Engel
OBJECTIVE: ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy...
July 21, 2017: Epilepsia
https://www.readbyqxmd.com/read/28733707/angiotensin-ii-type-1-receptor-blockers-inhibit-kat-ii-activity-in-the-brain-its-possible-clinical-applications
#2
Izabela Zakrocka, Katarzyna M Targowska-Duda, Artur Wnorowski, Tomasz Kocki, Krzysztof Jóźwiak, Waldemar A Turski
Angiotensin II receptor blockers (ARBs) are one of the most frequently recommended antihypertensive drugs. Apart from their activity towards the circulatory system, ARBs also penetrate the blood-brain barrier and display neuroprotective effects. Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan produced by kynurenine aminotransferase II (KAT II) in the brain. Antagonism towards all ionotropic glutamate (GLU) receptors is the main mechanism of KYNA action. An elevated brain level of KYNA is linked with memory impairment and psychotic symptoms...
July 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28733356/steady-state-free-ca2-in-astrocytes-is-decreased-by-experience-and-impacts-arteriole-tone
#3
Eslam M F Mehina, Ciaran Murphy-Royal, Grant R Gordon
Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca2+ activity. However, whether resting astrocyte Ca2+ can adjust to a new steady-state level, with an impact on surrounding brain cells, remains unknown. Using two-photon Ca2+ imaging in male rat acute brain slices of the somatosensory neocortex, we found that theta burst neural activity produced an unexpected long-lasting reduction in astrocyte free Ca2+ in the soma and endfeet. The drop in intracellular Ca2+ was attenuated by antagonists targeting multiple ionotropic and metabotropic glutamate receptors, and intracellular cascades involved Ca2+ stores and nitric oxide...
July 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28730825/the-implication-of-ampa-receptor-in-synaptic-plasticity-impairment-and-intellectual-disability-in-fragile-x-syndrome
#4
G-R Cheng, X-Y Li, Y-D Xiang, D Liu, S M McClintock, Y Zeng
Fragile X syndrome (FXS) is the most frequently inherited form of intellectual disability and prevalent single-gene cause of autism. A priority of FXS research is to determine the molecular mechanisms underlying the cognitive and social functioning impairments in humans and the FXS mouse model. Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate a majority of fast excitatory neurotransmission in the central nervous system and are critically important for nearly all aspects of brain function, including neuronal development, synaptic plasticity, and learning and memory...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28728214/p2x-receptor-channels-in-chronic-pain-pathways
#5
REVIEW
Louis-Philippe Bernier, Ariel R Ase, Philippe Séguéla
Chronic pain is a highly prevalent debilitating condition for which treatment options remain limited for many patients. Ionotropic ATP signaling through excitatory and calcium-permeable P2X receptor-channels is now rightfully considered as a critical player in pathological pain generation and maintenance, therefore their selective targeting represents a therapeutic opportunity with promising yet untapped potential. Recent advances in the structural, functional and pharmacological characterization of rodent and human ATP-gated P2X receptor-channels have shed brighter light on the role of specific subtypes in the pathophysiology of chronic inflammatory, neuropathic or cancer pain...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28726484/annals-express-experience-with-newer-central-nervous-system-autoantibodies
#6
Abid Karim, Saiju Jacob
In the last decade, a large number of neuronal cell-surface antibodies have been described which are responsible for a range of neuroimmunological central nervous system disorders. Unlike the paraneoplastic antibodies which target intracellular antigens, these antibodies appear to be pathogenic and hence identification and prompt treatment can make a substantial impact on clinical outcomes of these patients. We review the common antibodies against the ionotropic Glutamate receptors (NMDAR, AMPAR), metabotropic Glutamate receptors (mGluR1 and mGluR5), voltage gated potassium channel-complex proteins (LGI1, CASPR2), and other antibodies targeted against Glycine receptor, Glutamic acid decarboxylase (GAD), Gamma Amino Butyric Acid B (GABAB), Dopamine-2-receptor (D2R) and Dipeptidyl-peptidase-like protein 6 (DPPX)...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28726106/arginine-derivatives-of-dicarboxylic-acids-from-the-parotid-gland-secretions-of-common-toad-bufo-bufo-new-agonists-of-ionotropic-%C3%AE-aminobutyric-acid-receptors
#7
D S Lebedev, I A Ivanov, E V Kryukova, V G Starkov, V I Tsetlin, Yu N Utkin
Compounds activating γ-aminobutyric acid type A receptor were isolated from the toad Bufo bufo venom as a result of chromatographic separation. Analysis of the structure of these compounds by mass spectrometry and nuclear magnetic resonance showed that they are arginine derivatives of dicarboxylic acids and represent suberylarginine, pimeloylarginine, and adipoylarginine.
May 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28720963/releasing-characteristics-of-anthocyanins-extract-in-pectin-whey-protein-complex-microcapsules-coated-with-zein
#8
Arranee Chotiko, Subramaniam Sathivel
This study investigated pectin-based capsules as delivery systems for purple rice bran anthocyanin extract (AE) during exposure to simulated gastrointestinal conditions. Four different capsules loaded with AE were prepared by ionotropic gelation/extrusion, including (1) pectin capsules (PE), (2) pectin capsules coated with zein (PE/ZE), (3) pectin-whey protein isolate complex capsules (PE + WP), and (4) pectin-whey protein isolate complex capsules coated with zein (PE + WP/ZE). CaCl2 in an ethanol solution with or without zein was used as a crosslinking solution...
June 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28717974/improvement-of-oral-bioavailability-of-lopinavir-without-co-administration-of-ritonavir-using-microspheres-of-thiolated-xyloglucan
#9
Ashwini R Madgulkar, Mangesh R Bhalekar, Ashwini A Kadam
Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T80, surface morphology, and mucoadhesion employing in vitro wash off test...
July 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28715390/mammalian-cell-encapsulation-in-alginate-beads-using-a-simple-stirred-vessel
#10
Corinne A Hoesli, Roger L J Kiang, Kamini Raghuram, René G Pedroza, Karen E Markwick, Antonio M R Colantuoni, James M Piret
Cell encapsulation in alginate beads has been used for immobilized cell culture in vitro as well as for immunoisolation in vivo. Pancreatic islet encapsulation has been studied extensively as a means to increase islet survival in allogeneic or xenogeneic transplants. Alginate encapsulation is commonly achieved by nozzle extrusion and external gelation. Using this method, cell-containing alginate droplets formed at the tip of nozzles fall into a solution containing divalent cations that cause ionotropic alginate gelation as they diffuse into the droplets...
June 29, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28714086/n-glycan-content-modulates-kainate-receptor-functional-properties
#11
Claire G Vernon, Bryan A Copits, Jacob R Stolz, Yomayra F Guzmán, Geoffrey T Swanson
Ionotropic glutamate receptors (iGluRs) are tetrameric proteins with between 4 and 12 consensus sites for N-glycosylation on each subunit, which potentially allows for a high degree of structural diversity conferred by this post-translational modification. N-glycosylation is required for proper folding of iGluRs in mammalian cells, but the impact of oligosaccharides on the function of successfully folded receptors is less clear. Glycan moieties are large, polar, occasionally charged, and mediate many protein-protein interactions throughout the nervous system...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28701546/fast-voltage-sensitive-dye-imaging-of-excitatory-and-inhibitory-synaptic-transmission-in-the-rat-granular-retrosplenial-cortex
#12
Ken'ichi Nixima, Kazuo Okanoya, Noritaka Ichinohe, Tohru Kurotani
Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatio-temporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2-4 to layers 5-6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer...
July 12, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28701513/the-prion-protein-regulates-glutamate-mediated-ca-2-entry-and-mitochondrial-ca-2-accumulation-in-neurons
#13
Agnese De Mario, Caterina Peggion, Maria Lina Massimino, Francesca Viviani, Angela Castellani, Marta Giacomello, Dmitry Lim, Alessandro Bertoli, Maria Catia Sorgato
The prion protein, PrP(C), whose conformational misfolding originates deadly prions, has a still unclarified cellular function despite decades of intensive research. Following our recent finding that PrP(C) limits Ca(2+) entry via store-operated Ca(2+) channels in neurons, we investigated whether the protein could also control the activity of ionotropic glutamate receptors (iGluRs). To this end, we compared local Ca(2+) movements in primary cerebellar granule neurons and cortical neurons, expressing, or not, PrP(C), transduced with genetically encoded Ca(2+) probes...
July 12, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28696026/a-genome-wide-association-study-for-a-proxy-of-intermuscular-fat-level-in-the-italian-large-white-breed-identifies-genomic-regions-affecting-an-important-quality-parameter-for-dry-cured-hams
#14
L Fontanesi, G Schiavo, G Galimberti, S Bovo, V Russo, M Gallo, L Buttazzoni
Intermuscular fat content in protected designations of origin dry-cured hams is a very important meat quality trait that affects the acceptability of the product by the consumers. An excess in intermuscular fat (defined as the level of fat deposition between leg muscles) is a defect that depreciates the final product. In this study we carried out a genome-wide association study for visible intermuscular fat (VIF) of hams in the Italian Large White pig breed. This trait was evaluated on the exposed muscles of green legs in 1122 performance-tested gilts by trained personnel, according to a classification scale useful for routine and cheap evaluation...
August 2017: Animal Genetics
https://www.readbyqxmd.com/read/28693266/knockdown-of-glua2-induces-apoptosis-in-non-small-cell-lung-cancer-a549-cells-through-the-p53-signaling-pathway
#15
Hong-Yan Zhang, Wei Yang, Ji-Bin Lu
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors that mediate fast excitatory synaptic transmission in the brain. Previous studies have demonstrated that glutamate ionotropic receptor AMPA type subunit 2 (GluA2), one of the four subunits that comprise AMPA receptors, is a potential novel marker for poor prognosis in patients with human lung cancer. However, the mechanisms of GluA2-induced apoptosis, proliferation and migration in lung cancer remain unknown...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691798/structure-and-affinity-of-two-bicyclic-glutamate-analogues-at-ampa-and-kainate-receptors
#16
Stine Møllerud, Andrea Pinto, Laura Marconi, Karla Frydenvang, Thor S Thorsen, Saara K Laulumaa, Raminta Venskutonyte, Sebastian Winther, Ana M C Moral, Lucia Tamborini, Paola Conti, Darryl S Pickering, Jette Sandholm Kastrup
Ionotropic glutamate receptors (iGluRs) are involved in most of the fast excitatory synaptic transmission in the central nervous system. These receptors are important for learning and memory formation, but are also involved in the development of diseases such as Alzheimer's disease, epilepsy and depression. In order to understand the function of different types of iGluRs, selective agonists are invaluable as pharmacological tool compounds. Here, we report binding affinities of two bicyclic, conformationally restricted analogues of glutamate (CIP-AS and LM-12b) at AMPA (GluA2 and GluA3) and kainate receptor subunits (GluK1-3 and GluK5)...
July 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28688948/kondogogu-gum-zn-2-pectinate-emulgel-matrices-reinforced-with-mesoporous-silica-for-intragastric-furbiprofen-delivery
#17
Hriday Bera, Jhansirani Nadimpalli, Sanoj Kumar, Pavani Vengala
Flurbiprofen (FLU), a non-steroidal anti-inflammatory drug, exhibits limited clinical response due to its poor physicochemical properties. This study aimed at developing reliable drug carriers for intrgastric FLU delivery with a view to improve biopharmaceutical characteristics of drug and modulate its release in a controlled manner. In this context, FLU-loaded kondogogu gum (KG)-Zn(+2)-low methoxyl (LM) pectinate emulgel matrices reinforced with calcium silicate (CS) were accomplished by ionotropic gelation technique employing zinc acetate as cross-linker and characterized for their in vitro performances...
July 5, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28663723/huntingtin-interacting-protein-1-related-protein-plays-a-critical-role-in-dendritic-development-and-excitatory-synapse-formation-in-hippocampal-neurons
#18
Lin Peng, Qian Yang, Xingxing Xu, Yonglan Du, Yu Wu, Xiaofang Shi, Junyu Xu, Lijun Zhu, Jianhong Luo
Huntingtin-interacting protein 1-related (HIP1R) protein is considered to be an endocytic adaptor protein like the other two members of the Sla2 family, Sla2p and HIP1. They all contain homology domains responsible for the binding of clathrin, inositol lipids and F-actin. Previous studies have revealed that HIP1R is highly expressed in different regions of the mouse brain and localizes at synaptic structures. However, the function of HIP1R in the nervous system remains unknown. In this study, we investigated HIP1R function in cultured rat hippocampal neurons using an shRNA knockdown approach...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28658618/a-presynaptic-glutamate-receptor-subunit-confers-robustness-to-neurotransmission-and-homeostatic-potentiation
#19
Beril Kiragasi, Joyce Wondolowski, Yan Li, Dion K Dickman
Homeostatic signaling systems are thought to interface with other forms of plasticity to ensure flexible yet stable levels of neurotransmission. The role of neurotransmitter receptors in this process, beyond mediating neurotransmission itself, is not known. Through a forward genetic screen, we have identified the Drosophila kainate-type ionotropic glutamate receptor subunit DKaiR1D to be required for the retrograde, homeostatic potentiation of synaptic strength. DKaiR1D is necessary in presynaptic motor neurons, localized near active zones, and confers robustness to the calcium sensitivity of baseline synaptic transmission...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28656001/two-olfactory-pathways-to-detect-aldehydes-on-locust-mouthpart
#20
Liwei Zhang, Hongwei Li, Long Zhang
Sensing chemical cues is crucial for insects through their olfactory systems to adapt the environments. The receptors employed in insect olfactory system belong to the Odorant Receptor (ORs) and Ionotropic Receptor (IRs) families. In general, ORs and IRs are present in distinct olfactory sensory neurons and function independently. Here, we present evidence that in locust, the abundant host plant odor Hexanal is detected by both IR- and OR-expressing neurons. Use of the palp opening response (POR) as a simple behavioral paradigm in conjunction with RNA interference (RNAi) revealed that these two pathways are both needed for the detection of Hexanal...
2017: International Journal of Biological Sciences
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