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kainate receptor

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https://www.readbyqxmd.com/read/28636947/assembly-secretory-pathway-trafficking-and-surface-delivery-of-kainate-receptors-is-regulated-by-neuronal-activity
#1
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
https://www.readbyqxmd.com/read/28636281/aryl-and-heteroaryl-substituted-phenylalanines-as-ampa-receptor-ligands
#2
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/28631555/grik3-a-novel-oncogenic-protein-related-to-tumor-tnm-stage-lymph-node-metastasis-and-poor-prognosis-of-gc
#3
Baocheng Gong, Yuan Li, Zhenguo Cheng, Pengliang Wang, Lei Luo, Hanwei Huang, Shijie Duan, Funan Liu
Glutamate receptor, ionotropic, kainate 3 (GRIK3), as a member of the glutamate kainate receptor family, mainly participated in neuroactive ligand receptor interaction pathway. Other members of GRIK family were previously reported to regulate cellular migration, transformation, and proliferation in tumor. However, the mechanism of GRIK3 in tumor is still unclear. Therefore, the purpose of our study was to reveal the expression and clinical significance of GRIK3 in gastric cancer (GC). First, we performed the expression analysis and survival analysis of GRIK3 using The Cancer Genome Atlas (TCGA) database, and the results showed that the GRIK3 expressed differentially between gastric cancer tissues and the adjacent normal tissues and that higher expression of GRIK3 was associated with poor survival outcomes...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28603024/functional-research-and-molecular-mechanism-of-kainic-acid-induced-denitrosylation-of-thioredoxin-1-in-rat-hippocampus
#4
Hongning Yang, Ningjun Zhao, Lanxin Lv, Xianliang Yan, Shuqun Hu, Tie Xu
Thioredoxin-1 (Trx1) has long been recognized as a redox regulator, and is implicated in the inhibition of cell apoptosis. Trx1 is essential for the maintenance of the S-nitrosylation of molecules in cells. The S-nitrosylation of Trx1 is essential for the physiological function such as preservation of the redox regulatory activity. The mechanisms underlying Trx1 denitrosylation induced by kainate acid (KA) injection still remain uncharacterized. Our results showed that the S-nitrosylation levels of Trx1 were decreased subsequent to KA injection and that the glutamate receptor 6 (GluR6) antagonist NS102 could inhibit the denitrosylation of Trx1...
June 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28583584/common-variants-in-grik4-and-major-depressive-disorder-an-association-study-in-the-chinese-han-population
#5
Decheng Ren, Yan Bi, Fei Xu, Weibo Niu, Rui Zhang, Jiaxin Hu, Zhenming Guo, Xi Wu, Yanfei Cao, Xiaoye Huang, Fengping Yang, Lu Wang, Weidong Li, Yifeng Xu, Lin He, Tao Yu, Guang He, Xingwang Li
Major depressive disorder (MDD) is a common and complex mental disorder. Recent studies found that genetic variants located in GRIK4, which encoded glutamate ionotropic receptor kainate type subunit 4, was associated with the MDD. In this study, we intended to investigate whether GRIK4 gene was associated with MDD. So five single nucleotide polymorphisms (SNPs) were selected and genotyped (rs79526501, rs11218016, rs4582985, rs6589847, rs56275759) in 568 MDD patients and 846 healthy controls from Chinese Han population...
June 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28554163/the-influence-of-temperature-on-adult-zebrafish-sensitivity-to-pentylenetetrazole
#6
Fabiano Peres Menezes, Rosane Souza Da Silva
Pentylenetetrazole (PTZ) is one of the most valuable drugs used to induce seizure-like state in zebrafish especially considering the pharmacological screening for anticonvulsants and the study of basic mechanisms of epilepsy. Here, the effect of gender, weight and changes in temperature on latency to adult zebrafish reach classical seizure states induced by PTZ (10mM) was evaluated. Gender and weight (200-250mg versus 400-500mg) did not affect the profile of response to PTZ. When water temperature was changed from 22 to 30°C the lower temperature increased the latency time to reach seizure states and the higher temperature significantly decreased it, in comparison to the control group maintained at 26°C...
May 22, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28522210/novel-trigeminal-slice-preparation-method-for-studying-mechanisms-of-nociception-transmission
#7
Mikiko Hirahara, Naoshi Fujiwara, Kenji Seo
BACKGROUND: The trigeminal subnucleus caudalis (Vc) plays a critical role in transmission and modulation of nociceptive afferent inputs, and exhibits a similar layer construction to the spinal dorsal horn. However, afferent inputs enter the brainstem and project to a separately located nucleus. It has previously been difficult to record responses of the Vc to afferent fiber activation in a brainstem slice preparation. The aim of the present study was to establish a novel brainstem slice preparation method to study trigeminal nociceptive transmission mechanisms...
May 15, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28521778/cortical-kainate-receptors-and-behavioral-anxiety
#8
REVIEW
Min Zhuo
The study of glutamatergic synapses mainly focuses on the memory-related hippocampus. Recent studies in the cortical areas such as the anterior cingulate cortex (ACC) show that excitatory synapses can undergo long-term plastic changes in adult animals. Long-term potentiation (LTP) of cortical synapses may play important roles in chronic pain and anxiety. In addition to NMDA and AMPA receptors, kainate (KA) receptors have been found to play roles in synaptic transmission, regulation and presynaptic forms of LTP...
May 18, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28521126/structural-and-functional-architecture-of-ampa-type-glutamate-receptors-and-their-auxiliary-proteins
#9
REVIEW
Ingo H Greger, Jake F Watson, Stuart G Cull-Candy
AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction elements at synapses and are critical for the expression of plasticity. The kinetic and conductance properties of AMPARs are laid down during their biogenesis and are regulated by post-transcriptional RNA editing, splice variation, post-translational modification, and subunit composition...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28495313/posterior-hypothalamus-glutamate-infusion-decreases-pentylenetetrazol-induced-seizures-of-male-rats-through-hippocampal-histamine-increase
#10
Atieh Arzhang, Mahmoud Elahdadi Salmani, Taghi Lashkarbolouki, Iran Goudarzi
OBJECTIVES: Seizures are epileptic manifestations that are intrinsically modulated through different neurotransmitters and receptor systems. Although glutamate increases excitation and hence seizures, it activates other systems which could potentially terminate seizures. Histamine originates from neurons of the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but the effect of local PH glutamate on hippocampal histamine content is unknown. Therefore, in this study, the effect of PH glutamate and the involvement of hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was studied...
July 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28485896/shh-signalling-mediates-astrocyte-crosstalk-with-neurons-to-confer-neuroprotection
#11
Christopher I Ugbode, Imogen Smith, Benjamin J Whalley, Warren D Hirst, Marcus Rattray
Sonic Hedgehog (SHH) is a glycoprotein associated with development that is also expressed in the adult CNS and released after brain injury. Since the SHH receptors PTCH1 (patched homolog-1) and SMO (Smoothened) are highly expressed on astrocytes, we hypothesised that SHH regulates astrocyte function. Primary mouse cortical astrocytes derived from embryonic (E15) Swiss mouse cortices, were treated with two chemically distinct agonists of the SHH pathway, which caused astrocytes to elongate and proliferate. These changes are accompanied by decreases in the major astrocyte glutamate transporter, GLT-1 and the astrocyte intermediate filament protein GFAP...
May 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28475556/high-concentrations-of-tranexamic-acid-inhibit-ionotropic-glutamate-receptors
#12
Irene Lecker, Dian-Shi Wang, Kirusanthy Kaneshwaran, C David Mazer, Beverley A Orser
BACKGROUND: The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors...
July 2017: Anesthesiology
https://www.readbyqxmd.com/read/28459140/dynamical-differences-of-hemoglobin-and-the-ionotropic-glutamate-receptor-in-different-states-revealed-by-a-new-dynamics-alignment-method
#13
Dror Tobi
A new algorithm for comparison of protein dynamics is presented. Compared protein structures are superposed and their modes of motions are calculated using the Anisotropic Network Model. The obtained modes are aligned using the dynamic programming algorithm of Needleman and Wunsch, commonly used for sequence alignment. Dynamical comparison of Hemoglobin in the T and R2 states reveals that the dynamics of the allosteric effector 2,3-Bisphosphoglycerate binding site is different in the two states. These differences can contribute to the selectivity of the effector to the T state...
April 29, 2017: Proteins
https://www.readbyqxmd.com/read/28458040/temporal-and-spatial-dynamics-of-peripheral-afferent-evoked-activity-in-the-dorsal-horn-recorded-in-rat-spinal-cord-slices
#14
Fang Yu, Zhen-Yu Zhao, Ting He, Yao-Qing Yu, Zhen Li, Jun Chen
In the present study, multi-electrode array recording was used to examine dorsal horn activity following stimulation of primary afferents in a rat dorsal root attached-spinal cord slice preparation. The multi-electrode array probe was placed under the dorsal horn slice and local field potentials evoked by stimulation on the dorsal root were analyzed. Three kinds of dorsal root-evoked responses were identified. In lamina IIo, local field potentials exhibited P1 (peak latency 1.46±0.08ms), N1 (2.77±0.18ms, n=12), N2 (7...
May 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28455101/sip-1-mutations-cause-disturbances-in-the-activity-of-nmda-and-ampa-but-not-kainate-receptors-of-neurons-in-the-cerebral-cortex
#15
Maria V Turovskaya, Alexei A Babaev, Valery P Zinchenko, Ekaterina A Epifanova, Ekaterina V Borisova, Victor S Tarabykin, Egor A Turovsky
Smad-interacting protein-1 (Sip1) [Zinc finger homeobox (Zfhx1b), Zeb2] is a transcription factor implicated in the genesis of Mowat-Wilson syndrome (MWS) in humans. MWS is a rare genetic autosomal dominant disease caused by a mutation in the Sip1 gene (aka Zeb2 or Zfhx1b) mapped to 2q22.3 locus. MWS affects 1 in every 50-100 newborns worldwide. It is characterized by mental retardation, small stature, typical facial abnormalities as well as disturbances in the development of the cardio-vascular and renal systems as well as some other organs...
April 25, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28438504/agomelatine-protects-against-neuronal-damage-without-preventing-epileptogenesis-in-the-kainate-model-of-temporal-lobe-epilepsy
#16
Jana Tchekalarova, Dimitrinka Atanasova, Zlatina Nenchovska, Milena Atanasova, Lidia Kortenska, Rumyana Gesheva, Nikolai Lazarov
Recent studies about the novel antidepressant agomelatine, which is a mixed MT1 and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-induced memory impairment. In order to ascertain whether protection of some brain structures could suppress epileptogenesis, in the present study, we evaluated the effect of chronic post-status treatment with agomelatine on epileptogenesis, behavioral and neuronal damage induced by kainate acid (KA) status epilepticus (SE)...
April 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28418868/grik2-has-a-role-in-the-maintenance-of-urothelial-carcinoma-stem-like-cells-and-its-expression-is-associated-with-poorer-prognosis
#17
Ryuta Inoue, Yoshihiko Hirohashi, Hiroshi Kitamura, Sachiyo Nishida, Aiko Murai, Akari Takaya, Eri Yamamoto, Masahiro Matsuki, Toshiaki Tanaka, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Noriyuki Sato, Naoya Masumori, Toshihiko Torigoe
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are small sub-population of cancer cells that are endowed with higher tumor-initiating ability, self-renewal ability and differentiation ability. CSCs/CICs could be isolated as high aldehyde dehydrogenase 1 activity cells (ALDH1high) from various cancer samples. In this study, we isolated urothelial carcinoma CSCs/CICs as ALDHhigh cells and investigated the molecular aspects. ALDH1high cells showed greater sphere-forming ability and higher tumor-initiating ability in immune-deficient mice than those of ALDH1low cells, indicating that CSCs/CICs were enriched in ALDH1high cells...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412965/multireceptor-fingerprints-in-progressive-supranuclear-palsy
#18
Wang Zheng Chiu, Laura Donker Kaat, Agnita J W Boon, Wouter Kamphorst, Axel Schleicher, Karl Zilles, John C van Swieten, Nicola Palomero-Gallagher
BACKGROUND: Progressive supranuclear palsy (PSP) with a frontal presentation, characterized by cognitive deficits and behavioral changes, has been recognized as an early clinical picture, distinct from the classical so-called Richardson and parkinsonism presentations. The midcingulate cortex is associated with executive and attention tasks and has consistently been found to be impaired in imaging studies of patients with PSP. The aim of the present study was to determine alterations in neurotransmission underlying the pathophysiology of PSP, as well as their significance for clinically identifiable PSP subgroups...
April 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28403176/faster-flux-of-neurotransmitter-glutamate-during-seizure-evidence-from-13c-enrichment-of-extracellular-glutamate-in-kainate-rat-model
#19
Keiko Kanamori
The objective is to examine how the flux of neurotransmitter glutamate from neurons to the extracellular fluid, as measured by the rate of 13C enrichment of extracellular glutamate (GLUECF), changes in response to seizures in the kainate-induced rat model of temporal-lobe epilepsy. Following unilateral intrahippocampal injection of kainate, GLUECF was collected by microdialysis from the CA1/CA3 region of awake rats, in combination with EEG recording of chronic-phase recurrent seizures and intravenous infusion of [2,5-13C]glucose...
2017: PloS One
https://www.readbyqxmd.com/read/28393897/olanzapine-but-not-clozapine-increases-glutamate-release-in-the-prefrontal-cortex-of-freely-moving-mice-by-inhibiting-d-aspartate-oxidase-activity
#20
Silvia Sacchi, Vito De Novellis, Giovanna Paolone, Tommaso Nuzzo, Monica Iannotta, Carmela Belardo, Marta Squillace, Paolo Bolognesi, Elena Rosini, Zoraide Motta, Martina Frassineti, Alessandro Bertolino, Loredano Pollegioni, Michele Morari, Sabatino Maione, Francesco Errico, Alessandro Usiello
D-aspartate levels in the brain are regulated by the catabolic enzyme D-aspartate oxidase (DDO). D-aspartate activates NMDA receptors, and influences brain connectivity and behaviors relevant to schizophrenia in animal models. In addition, recent evidence reported a significant reduction of D-aspartate levels in the post-mortem brain of schizophrenia-affected patients, associated to higher DDO activity. In the present work, microdialysis experiments in freely moving mice revealed that exogenously administered D-aspartate efficiently cross the blood brain barrier and stimulates L-glutamate efflux in the prefrontal cortex (PFC)...
April 10, 2017: Scientific Reports
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