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https://www.readbyqxmd.com/read/28442530/breach-of-autoreactive-b-cell-tolerance-by-post-translationally-modified-proteins
#1
Jacqueline S Dekkers, Marije K Verheul, Jeroen N Stoop, Bisheng Liu, Andreea Ioan-Facsinay, Peter A van Veelen, Arnoud H de Ru, George M C Janssen, Martin Hegen, Steve Rapecki, Tom W J Huizinga, Leendert A Trouw, René E M Toes
OBJECTIVES: Over 50% of patients with rheumatoid arthritis (RA) harbour a variety of anti-modified protein antibodies (AMPA) against different post-translationally modified (PTM) proteins, including anti-carbamylated protein (anti-CarP) antibodies. At present, it is unknown how AMPA are generated and how autoreactive B cell responses against PTM proteins are induced. Here we studied whether PTM foreign antigens can breach B cell tolerance towards PTM self-proteins. METHODS: Serum reactivity towards five carbamylated proteins was determined for 160 patients with RA and 40 healthy individuals...
April 25, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28442348/upregulation-of-neurotrophins-by-s-47445-a-novel-positive-allosteric-modulator-of-ampa-receptors-in-aged-rats
#2
Francesca Calabrese, Elisa Savino, Elisabeth Mocaer, Sylvie Bretin, Giorgio Racagni, Marco A Riva
At molecular levels, it has been shown that aging is associated with alterations in neuroplastic mechanisms. In this study, it was examined if the altered expression of neurotrophins observed in aged rats could be corrected by a chronic treatment with S 47445 (1-3-10mg/kg, p.o.), a novel selective positive allosteric modulator of the AMPA receptors. Both the mRNA and the protein levels of the neurotrophins Bdnf, NT-3 and Ngf were specifically measured in the prefrontal cortex and hippocampus (ventral and dorsal) of aged rats...
April 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28442196/mechanism-of-neuronal-activity-and-synaptic-transmission-in-rostral-ventrolateral-medulla
#3
Liangchen Zhao, Tianji Liu, Rutao Xu, Liu He, Man Duan, Dejun Xu
Rostral ventrolateral medulla (RVLM) plays an essential role in blood pressure homeostasis. This study was aimed to investigate the mechanism of neuronal activity and synaptic transmission in the RVLM. Medulla oblongata slices were carefully obtained from brainstem of rats. With continues perfusion of artificial cerebrospinal fluid (ACSF), the spontaneous firing of slices and amplitudes were assayed by conventional whole cell patch-clamp recording after addition of gamma-aminobutyric acid (GABA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl d-aspartate (NMDA)...
April 22, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28440221/nptx2-and-cognitive-dysfunction-in-alzheimer-s-disease
#4
Mei-Fang Xiao, Desheng Xu, Michael T Craig, Kenneth A Pelkey, Chun-Che Chien, Yang Shi, Juhong Zhang, Susan Resnick, Olga Pletnikova, David Salmon, James Brewer, Steven Edland, Jerzy Wegiel, Benjamin Tycko, Alena Savonenko, Roger H Reeves, Juan C Troncoso, Chris J McBain, Douglas Galasko, Paul F Worley
Memory loss in Alzheimer's disease (AD) is attributed to pervasive weakening and loss of synapses. Here, we present findings supporting a special role for excitatory synapses connecting pyramidal neurons of the hippocampus and cortex with fast-spiking parvalbumin (PV) interneurons that control network excitability and rhythmicity. Excitatory synapses on PV interneurons are dependent on the AMPA receptor subunit GluA4, which is regulated by presynaptic expression of the synaptogenic immediate early gene NPTX2 by pyramidal neurons...
March 23, 2017: ELife
https://www.readbyqxmd.com/read/28432359/role-of-the-ion-channel-extracellular-collar-in-ampa-receptor-gating
#5
Maria V Yelshanskaya, Samaneh Mesbahi-Vasey, Maria G Kurnikova, Alexander I Sobolevsky
AMPA subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission and are implicated in numerous neurological diseases. Ionic currents through AMPA receptor channels can be allosterically regulated via different sites on the receptor protein. We used site-directed mutagenesis and patch-clamp recordings to probe the ion channel extracellular collar, the binding region for noncompetitive allosteric inhibitors. We found position and substitution-dependent effects for introduced mutations at this region on AMPA receptor gating...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428223/glutamatergic-mechanisms-involved-in-bladder-overactivity-and-pudendal-neuromodulation-in-cats
#6
Jamie Uy, Michelle Yu, Xuewen Jiang, Cameron Jones, Bing Shen, Jicheng Wang, James R Roppolo, William C de Groat, Changfeng Tai
The involvement of ionotropic glutamate receptors in bladder overactivity and pudendal neuromodulation was determined in α-chloralose anesthetized cats by intravenously administering MK801 (a NMDA receptor antagonist) or CP465022 (an AMPA receptor antagonist). Infusion of 0.5% acetic acid (AA) into the bladder produced bladder overactivity. In the first group of 5 cats, bladder capacity was significantly (p<0.05) reduced to 55.3±10.0% of saline control by AA irritation. Pudendal nerve stimulation (PNS) significantly (p<0...
April 20, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28425566/gender-specific-histopathological-response-in-guppies-poecilia-reticulata-exposed-to-glyphosate-or-its-metabolite-aminomethylphosphonic-acid
#7
Adriana Maria Antunes, Thiago Lopes Rocha, Fernando Santiago Pires, Meire Alves de Freitas, Vanessa Rafaela Milhomem Cruz Leite, Sarah Arana, Paulo César Moreira, Simone Maria Teixeira Sabóia-Morais
Ecotoxicity of glyphosate (GLY) and its metabolite aminomethylphosphonic acid (AMPA) was investigated in guppies, Poecilia reticulata. We tested the effects of these chemicals on the gills and liver of both male and female guppies using qualitative and quantitative histopathological analyses associated with histopathological condition indexes. Both genders showed similar median lethal concentration (LC50 ) at 96 h for GLY (68.78 and 70.87 mg l(-1) ) and AMPA (180 and 164.32 mg l(-1) ). However, the histopathological assessment of both fish organs exposed to sublethal concentrations of GLY (35 mg l(-1) ) and AMPA (82 mg l(-1) ) for 96 h showed a tissue- and gender-specific histopathological response...
April 20, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28419244/resolvin-d1-and-d2-reverse-lipopolysaccharide-induced-depression-like-behaviors-through-the-mtorc1-signaling-pathway
#8
Satoshi Deyama, Yuka Ishikawa, Kotomi Yoshikawa, Kento Shimoda, Soichiro Ide, Masamichi Satoh, Masabumi Minami
Background: Resolvin D1 (RvD1) and D2 (RvD2) are bioactive lipid mediators that are generated from docosahexaenoic acid (DHA). Although recent preclinical studies suggest that these compounds have antidepressant effects, their mechanisms of action remain unclear. Methods: We investigated mechanisms underlying the antidepressant effects of RvD1 and RvD2 in lipopolysaccharide (LPS; 0.8 mg/kg, i.p.)-induced depression model mice using a tail suspension test. Results: Intracerebroventricular (i...
April 13, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28418018/neurodevelopmental-changes-in-excitatory-synaptic-structure-and-function-in-the-cerebral-cortex-of-sanfilippo-syndrome-iiia-mice
#9
Chrissa A Dwyer, Samantha L Scudder, Ying Lin, Lara E Dozier, Dustin Phan, Nicola J Allen, Gentry N Patrick, Jeffrey D Esko
Sanfilippo syndrome, MPS IIIA-D, results from deficits in lysosomal enzymes that specifically degrade heparan sulfate, a sulfated glycosaminoglycan. The accumulation of heparan sulfate results in neurological symptoms, culminating in extensive neurodegeneration and early death. To study the impact of storage in postnatal neurodevelopment, we examined murine models of MPS IIIA, which lack the enzyme sulfamidase. We show that changes occur in excitatory postsynaptic structure and function in the somatosensory cortex prior to signs of neurodegeneration...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28412220/inflammation-induced-glua1-trafficking-and-membrane-insertion-of-ca-2-permeable-ampa-receptors-in-dorsal-horn-neurons-is-dependent-on-spinal-tumor-necrosis-factor-pi3-kinase-and-protein-kinase-a
#10
G Wigerblad, J R Huie, H Z Yin, M Leinders, R A Pritchard, F J Koehrn, W-H Xiao, G J Bennett, R L Huganir, A R Ferguson, J H Weiss, C I Svensson, L S Sorkin
Peripheral inflammation induces sensitization of nociceptive spinal cord neurons. Both spinal tumor necrosis factor (TNF) and neuronal membrane insertion of Ca(2+) permeable AMPA receptor (AMPAr) contribute to spinal sensitization and resultant pain behavior, molecular mechanisms connecting these two events have not been studied in detail. Intrathecal (i.t.) injection of TNF-blockers attenuated paw carrageenan-induced mechanical and thermal hypersensitivity. Levels of GluA1 and GluA4 from dorsal spinal membrane fractions increased in carrageenan-injected rats compared to controls...
April 12, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28411409/dynamic-imaging-of-ampa-receptor-trafficking-in-vitro-and-in-vivo
#11
REVIEW
Richard H Roth, Yong Zhang, Richard L Huganir
Modulation of synaptic strength through trafficking of AMPA receptors is a fundamental mechanism underlying synaptic plasticity and has been shown to be an important process in higher brain functions such as learning and memory. Many studies have used live time-lapse imaging of fluorescently tagged AMPA receptors to directly monitor their membrane trafficking in the basal state as well as during synaptic plasticity. While most of these studies are performed in vitro using neuronal cell cultures, in the past years technological advances have enabled the imaging of synaptic proteins in vivo in intact organisms...
April 12, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28408870/homeostatic-changes-in-gaba-and-glutamate-receptors-on-excitatory-cortical-neurons-during-sleep-deprivation-and-recovery
#12
Esther Del Cid-Pellitero, Anton Plavski, Lynda Mainville, Barbara E Jones
Neuronal activity is regulated in a homeostatic manner through changes in inhibitory GABA and excitatory glutamate (Glu) AMPA (A) receptors (GluARs). Using immunofluorescent staining, we examined whether calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)-labeled (+) excitatory neurons in the barrel cortex undergo such homeostatic regulation following enforced waking with associated cortical activation during the day when mice normally sleep the majority of the time. Sleep deprived mice were prevented from falling asleep by unilateral whisker stimulation and sleep recovery (SR) mice allowed to sleep freely following deprivation...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28407141/sensory-deprivation-triggers-synaptic-and-intrinsic-plasticity-in-the-hippocampus
#13
Hila Milshtein-Parush, Samuel Frere, Limor Regev, Coren Lahav, Amit Benbenishty, Shamgar Ben-Eliyahu, Inbal Goshen, Inna Slutsky
Hippocampus, a temporal lobe structure involved in learning and memory, receives information from all sensory modalities. Despite extensive research on the role of sensory experience in cortical map plasticity, little is known about whether and how sensory experience regulates functioning of the hippocampal circuits. Here, we show that 9 ± 2 days of whisker deprivation during early mouse development depresses activity of CA3 pyramidal neurons by several principal mechanisms: decrease in release probability, increase in the fraction of silent synapses, and reduction in intrinsic excitability...
April 12, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28404824/glycolytic-inhibition-by-2-deoxy-d-glucose-abolishes-both-neuronal-and-network-bursts-in-an-in-vitro-seizure-model
#14
Li-Rong Shao, Carl E Stafstrom
Neuronal activity is energy demanding and coupled to cellular metabolism. In this study, we investigated the effects of glycolytic inhibition with 2-deoxy-D-glucose (2-DG) on basal membrane properties, spontaneous neuronal firing, and epileptiform network bursts in hippocampal slices. The effect of glycolytic inhibition on basal membrane properties was examined in hippocampal CA1 neurons, which are not ordinarily active spontaneously. Intracellular application of 2-DG did not significantly alter the membrane input resistance, action-potential threshold, firing pattern or input-output relationship of these neurons compared with simultaneously recorded neighboring neurons without intracellular 2-DG...
April 12, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28401767/expanded-target-chemical-analysis-reveals-extensive-mixed-organic-contaminant-exposure-in-u-s-streams
#15
Paul M Bradley, Celeste A Journey, Kristin M Romanok, Larry B Barber, Herbert T Buxton, William T Foreman, Edward T Furlong, Susan T Glassmeyer, Michelle L Hladik, Luke R Iwanowicz, Daniel K Jones, Dana W Kolpin, Kathryn M Kuivila, Keith A Loftin, Marc A Mills, Michael T Meyer, James L Orlando, Timothy J Reilly, Kelly L Smalling, Daniel L Villeneuve
Surface water from 38 streams nationwide was assessed using 14 target-organic methods (719 compounds). Designed-bioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10 most-frequently detected anthropogenic-organics included eight pesticides (desulfinylfipronil, AMPA, chlorpyrifos, dieldrin, metolachlor, atrazine, CIAT, glyphosate) and two pharmaceuticals (caffeine, metformin) with detection frequencies ranging 66-84% of all sites. Detected contaminant concentrations varied from less than 1 ng L(-1) to greater than 10 μg L(-1), with 77 and 278 having median detected concentrations greater than 100 ng L(-1) and 10 ng L(-1), respectively...
April 12, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28400815/delayed-treatment-of-secondary-degeneration-following-acute-optic-nerve-transection-using-a-combination-of-ion-channel-inhibitors
#16
Nathanael J Yates, Marcus K Giacci, Ryan L O'Hare Doig, Wissam Chiha, Bethany E Ashworth, Jade Kenna, Carole A Bartlett, Melinda Fitzgerald
Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca(2+) entry-inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury site via an iPRECIO(@) pump immediately, 6 hours, 24 hours and 7 days after partial optic nerve transection surgery...
February 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28400714/deletion-of-trpc6-attenuates-nmda-receptor-mediated-ca-2-entry-and-ca-2-induced-neurotoxicity-following-cerebral-ischemia-and-oxygen-glucose-deprivation
#17
Jin Chen, Zhaozhong Li, Jeffery T Hatcher, Qing-Hui Chen, Li Chen, Robert D Wurster, Sic L Chan, Zixi Cheng
Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na(+) and Ca(2+) and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death. Using live-cell imaging to examine intracellular Ca(2+) levels ([Ca(2+)] i ), we found that OGD induced a significant higher increase in glutamate-evoked Ca(2+) influx compared to untreated control and such an increase was reduced by TRPC6 deletion...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28400532/papers-of-note-in-science356-6333
#18
Annalisa M VanHook
This week's articles identify a potential cause for the development of celiac disease and a method for targeting an AMPA receptor agonist to specific neurons.
April 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28400257/phase-amplitude-coupled-persistent-theta-and-gamma-oscillations-in-rat-primary-motor-cortex-in%C3%A2-vitro
#19
Nicholas W Johnson, Mazhar Özkan, Adrian P Burgess, Emma J Prokic, Keith A Wafford, Michael J O'Neill, Stuart D Greenhill, Ian M Stanford, Gavin L Woodhall
In vivo, theta (4-7 Hz) and gamma (30-80 Hz) neuronal network oscillations are known to coexist and display phase-amplitude coupling (PAC). However, in vitro, these oscillations have for many years been studied in isolation. Using an improved brain slice preparation technique we have, using co-application of carbachol (10 μM) and kainic acid (150 nM), elicited simultaneous theta (6.6 ± 0.1 Hz) and gamma (36.6 ± 0.4 Hz) oscillations in rodent primary motor cortex (M1). Each oscillation showed greatest power in layer V...
April 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28397107/the-number-and-distribution-of-ampa-receptor-channels-containing-fast-kinetic-glua3-and-glua4-subunits-at-auditory-nerve-synapses-depend-on-the-target-cells
#20
María E Rubio, Ko Matsui, Yugo Fukazawa, Naomi Kamasawa, Harumi Harada, Makoto Itakura, Elek Molnár, Manabu Abe, Kenji Sakimura, Ryuichi Shigemoto
The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus...
April 10, 2017: Brain Structure & Function
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