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https://www.readbyqxmd.com/read/28911857/new-mouse-model-for-inducing-and-evaluating-unilateral-vestibular-deafferentation-syndrome
#1
R Cassel, P Bordiga, D Pericat, C Hautefort, B Tighilet, C Chabbert
BACKGROUND: Unilateral vestibular deafferentation syndrome (uVDS) holds a particular place in the vestibular pathology domain. Due to its suddenness, the violence of its symptoms that often result in emergency hospitalization, and its associated original neurophysiological properties, this syndrome is a major source of questioning for the otoneurology community. Also, its putative pathogenic causes remain to be determined. There is currently a strong medical need for the development of targeted and effective countermeasures to improve the therapeutic management of uVDS...
September 11, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28891049/differential-projections-of-the-densocellular-and-intermediate-parts-of-the-hyperpallium-in-the-pigeon-columba-livia
#2
Yasuro Atoji, Sonjoy Sarkar, J Martin Wild
The visual Wulst in birds shows a four-layered structure: apical part of the hyperpallium (HA), interstitial part of HA (IHA), intercalated part of hyperpallium (HI), and densocellular part of hyperpallium (HD). HD also connects with the hippocampus and olfactory system. Because HD is subjacent to HI, the two have been treated as one structure in many studies, and the fiber connections of HD have been examined by afferents and efferents originating outside HD. However, to clarify the difference between these two layers, they need to be treated separately...
September 10, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28888867/pick1facilitates-lasting-reduction-in-glua2-concentration-in-the-hippocampus-during-chronic-epilepsy
#3
Jan-Øyvind Lorgen, Daniel Lawer Egbenya, Janniche Hammer, Svend Davanger
Overstimulation of glutamate receptors resulting in excessive intracellular calcium concentrations is a major cause of neuronal cell death in epilepsy. The main source of increased calcium concentration during this excitotoxicity is an influx through NMDA subtype of glutamate receptors. The GluR2 hypothesis states that following a neurological insult such as an epileptic seizure, the AMPAR subunit GluR2 protein is down regulated. This increases the likelihood of the formation of GluR2-lacking, calcium-permeable AMPARs which might further enhance the toxicity of the neurotransmitter, glutamate...
August 31, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28886144/pharmacological-characterisation-of-s-47445-a-novel-positive-allosteric-modulator-of-ampa-receptors
#4
Sylvie Bretin, Caroline Louis, Laure Seguin, Stéphanie Wagner, Jean-Yves Thomas, Sylvie Challal, Nathalie Rogez, Karine Albinet, Fabrice Iop, Nadège Villain, Sonia Bertrand, Ali Krazem, Daniel Bérachochéa, Stéphanie Billiald, Charles Tordjman, Alex Cordi, Daniel Bertrand, Pierre Lestage, Laurence Danober
S 47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPA-PAM). S 47445 enhanced glutamate's action at AMPA receptors on human and rat receptors and was inactive at NMDA and kainate receptors. Potentiation did not differ among the different AMPA receptors subtypes (GluA1/2/4 flip and flop variants) (EC50 between 2.5-5.4 μM), except a higher EC50 value for GluA4 flop (0.7 μM) and a greater amount of potentiation on GluA1 flop. A low concentration of S 47445 (0...
2017: PloS One
https://www.readbyqxmd.com/read/28872832/chemically-modified-%C3%AE-amino-3-hydroxy-5-methyl-4-isoxazole-ampa-receptor-rna-aptamers-designed-for-in-vivo-use
#5
Zhen Huang, Wei Wen, Andrew Wu, Li Niu
Glutamate ion channels have three subtypes, that is, α-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA), kainate, and N-methyl-d-aspartate (NMDA) receptors. Excessive activity of these receptor subtypes either individually or collectively is involved in various neurological disorders. RNA aptamers as antagonists of these receptors are potential therapeutics. For developing aptamer therapeutics, the RNA aptamers must be chemically modified to become ribonuclease-resistant or stable in biological fluids. Using systematic evolution of ligands by exponential enrichment (SELEX) and a chemically modified library, prepared enzymatically (i...
September 5, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28867067/corrigendum-to-prunetin-signals-via-g-protein-coupled-receptor-gpr30-stimulation-of-adenylyl-cyclase-and-camp-mediated-activation-of-mapk-signaling-induces-runx2-expression-in-osteoblasts-to-promote-bone-regeneration-j-nutr-biochem-2015-26-12-1491-501
#6
Kainat Khan, Subhashis Pal, Manisha Yadav, Rakesh Maurya, Arun Kumar Trivedi, Sabyasachi Sanyal, Naibedya Chattopadhyay
No abstract text is available yet for this article.
September 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28854365/neto-auxiliary-subunits-regulate-interneuron-somatodendritic-and-presynaptic-kainate-receptors-to-control-network-inhibition
#7
Megan S Wyeth, Kenneth A Pelkey, Xiaoqing Yuan, Geoffrey Vargish, April D Johnston, Steven Hunt, Calvin Fang, Daniel Abebe, Vivek Mahadevan, André Fisahn, Michael W Salter, Roderick R McInnes, Ramesh Chittajallu, Chris J McBain
Although Netos are considered auxiliary subunits critical for kainate receptor (KAR) function, direct evidence for their regulation of native KARs is limited. Because Neto KAR regulation is GluK subunit/Neto isoform specific, such regulation must be determined in cell-type-specific contexts. We demonstrate Neto1/2 expression in somatostatin (SOM)-, cholecystokinin/cannabinoid receptor 1 (CCK/CB1)-, and parvalbumin (PV)-containing interneurons. KAR-mediated excitation of these interneurons is contingent upon Neto1 because kainate yields comparable effects in Neto2 knockouts and wild-types but fails to excite interneurons or recruit inhibition in Neto1 knockouts...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28837400/80pkc-sumoylation-inhibits-the-binding-of-14-3-3%C3%AF-to-gluk2
#8
Xiaoling Li, Yan Wang, Aoxue Zhu, Jie Zhou, Yong Li
Phosphorylation and SUMOylation of the kainate receptor (KAR) subunit GluK2 have been shown to regulate KAR surface expression, trafficking and synaptic plasticity. In addition, our previous study has shown that a phosphorylation-dependent interaction of 14-3-3τ and GluK2a-containing receptors contributes to the slow decay kinetics of native KAR-EPSCs. However, it is unknown whether SUMOylation participates in the regulation of the interaction between 14-3-3τ and GluK2a-containing receptors. Here we report that SUMOylation of PKC, but not GluK2, represses the binding of 14-3-3τ to GluK2a via decreasing the phosphorylation level of GluK2a...
August 24, 2017: Channels
https://www.readbyqxmd.com/read/28804757/one-aptamer-two-functions-the-full-length-aptamer-inhibits-ampa-receptors-while-the-short-one-inhibits-both-ampa-and-kainate-receptors
#9
William J Jaremko, Zhen Huang, Wei Wen, Andrew Wu, Nicholas Karl, Li Niu
AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the Journal of Biological Chemistry by Jaremko et al. 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors...
2017: RNA & Disease
https://www.readbyqxmd.com/read/28795276/topiramate-via-nmda-ampa-kainate-gabaa-and-alpha2-receptors-and-by-modulation-of-creb-bdnf-and-akt-gsk3-signaling-pathway-exerts-neuroprotective-effects-against-methylphenidate-induced-neurotoxicity-in-rats
#10
Majid Motaghinejad, Manijeh Motevalian, Sulail Fatima, Tabassom Beiranvand, Shiva Mozaffari
Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABAA receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D2 receptor antagonist...
August 9, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28776308/susceptibility-to-soman-toxicity-and-efficacy-of-ly293558-against-soman-induced-seizures-and-neuropathology-in-10-month-old-male-rats
#11
James P Apland, Vassiliki Aroniadou-Anderjaska, Taiza H Figueiredo, Eric M Prager, Cara H Olsen, Maria F M Braga
Acute nerve agent exposure causes prolonged status epilepticus (SE), leading to death or long-term brain damage. We have previously demonstrated that LY293558, an AMPA/GluK1 kainate receptor antagonist, terminates SE induced by the nerve agent soman and protects from long-term brain damage, in immature rats and young-adult rats, even if administered with a relatively long latency from the time of exposure. However, susceptibility to the lethal consequences of SE increases with age, and mortality by SE induced by soman is substantially greater in older animals...
August 3, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28723387/sigma-1-receptor-activation-modifies-intracellular-calcium-exchange-in-the-g93a-hsod1-als-model
#12
Vedrana Tadić, Ayse Malci, Nadine Goldhammer, Beatrice Stubendorff, Saikata Sengupta, Tino Prell, Silke Keiner, Jingyu Liu, Madlen Guenther, Christiane Frahm, Otto W Witte, Julian Grosskreutz
Aberrations in intracellular calcium (Ca(2+)) have been well established within amyotrophic lateral sclerosis (ALS), a severe motor neuron disease. Intracellular Ca(2+) concentration is controlled in part through the endoplasmic reticulum (ER) mitochondria Ca(2+) cycle (ERMCC). The ER supplies Ca(2+) to the mitochondria at close contacts between the two organelles, i.e. the mitochondria-associated ER membranes (MAMs). The Sigma 1 receptor (Sig1R) is enriched at MAMs, where it acts as an inter-organelle signaling modulator...
July 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28717010/phosphorylation-of-the-kainate-receptor-kar-auxiliary-subunit-neto2-at-serine-409-regulates-synaptic-targeting-of-the-kar-subunit-gluk1
#13
Richa Madan Lomash, Nengyin Sheng, Yan Li, Roger A Nicoll, Katherine W Roche
Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits and post translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we find that the intracellular region of neuropilin and tolloid-like proteins (Neto)1 and Neto2, the auxiliary subunits of KARs are phosphorylated by multiple kinases in vitro...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28714086/n-glycan-content-modulates-kainate-receptor-functional-properties
#14
Claire G Vernon, Bryan A Copits, Jacob R Stolz, Yomayra F Guzmán, Geoffrey T Swanson
KEY POINTS: Ionotropic glutamate receptor (iGluR) subunits are N-glycosylated at 4-12 sites, and Golgi processing produces mature receptors that contain high-mannose, hybrid and complex oligosaccharides. N-glycosylation is crucial for receptor biogenesis, influences receptor trafficking and provides a binding site for carbohydrate binding proteins. Glycan moieties are large, polar and occasionally charged, and they are attached at sites along iGluRs that position them for involvement in the structural changes underlying gating...
September 1, 2017: Journal of Physiology
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
#15
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/28691798/structure-and-affinity-of-two-bicyclic-glutamate-analogues-at-ampa-and-kainate-receptors
#16
Stine Møllerud, Andrea Pinto, Laura Marconi, Karla Frydenvang, Thor Seneca Thorsen, Saara Laulumaa, Raminta Venskutonytė, Sebastian Winther, Ana Maria Cuñado 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. 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 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28680963/neto1-guides-development-of-glutamatergic-connectivity-in-the-hippocampus-by-regulating-axonal-kainate-receptors
#17
Ester Orav, Tsvetomira Atanasova, Alexandra Shintyapina, Sebnem Kesaf, Michela Kokko, Juha Partanen, Tomi Taira, Sari E Lauri
Kainate-type glutamate receptors (KARs) are highly expressed in the developing brain, where they are tonically activated to modulate synaptic transmission, network excitability and synaptogenesis. NETO proteins are auxiliary subunits that regulate biophysical properties of KARs; however, their functions in the immature brain are not known. Here, we show that NETO1 guides the development of the rodent hippocampal CA3-CA1 circuitry via regulating axonal KARs. NETO deficiency reduced axonal targeting of most KAR subunits in hippocampal neurons in a subtype independent manner...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28664455/neuroprotective-effects-of-the-absence-of-jnk1-or-jnk3-isoforms-on-kainic-acid-induced-temporal-lobe-epilepsy-like-symptoms
#18
Luisa de Lemos, Felix Junyent, Antoni Camins, Rubén Darío Castro-Torres, Jaume Folch, Jordi Olloquequi, Carlos Beas-Zarate, Ester Verdaguer, Carme Auladell
The activation of c-Jun-N-terminal kinases (JNK) pathway has been largely associated with the pathogenesis and the neuronal death that occur in neurodegenerative diseases. Altogether, this justifies why JNKs have become a focus of screens for new therapeutic strategies. The aim of the present study was to identify the role of the different JNK isoforms (JNK1, JNK2, and JNK3) in apoptosis and inflammation after induction of brain damage. To address this aim, we induced excitotoxicity in wild-type and JNK knockout mice (jnk1 (-/-) , jnk2 (-/-) , and jnk3 (-/-) ) via an intraperitoneal injection of kainic acid, an agonist of glutamic-kainate-receptors, that induce status epilepticus...
June 29, 2017: Molecular Neurobiology
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/28636947/assembly-secretory-pathway-trafficking-and-surface-delivery-of-kainate-receptors-is-regulated-by-neuronal-activity
#20
Ashley J Evans, Sonam Gurung, Kevin A Wilkinson, David J Stephens, Jeremy M Henley
Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity...
June 20, 2017: Cell Reports
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