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Ampa receptors

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https://www.readbyqxmd.com/read/28214854/microrna-183-suppresses-neuropathic-pain-and-expression-of-ampa-receptors-by-targeting-mtor-vegf-signaling-pathway
#1
Xiaojuan Xie, Ligang Ma, Kai Xi, Wei Zhang, Dongmei Fan
BACKGROUND: Neuropathic pain is a type of chronic pain that results from dysfunctions of the somatosensory nerve system. This study was aimed to investigate the effect of mTOR/VEGF signaling pathway on neuropathic pain and the regulation mechanisms of miR-183 on AMPA Receptors through mTOR/VEGF signaling pathway. METHODS: Chronic compress injury (CCI) model was constructed in the current study, we used paw withdrawal mechanic threshold (PWMT) and paw withdrawal thermal latency (PWTL) to observe mTOR and VEGF receptors...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28212375/epilepsy-associated-gene-nedd4-2-mediates-neuronal-activity-and-seizure-susceptibility-through-ampa-receptors
#2
Jiuhe Zhu, Kwan Young Lee, Kathryn A Jewett, Heng-Ye Man, Hee Jung Chung, Nien-Pei Tsai
The neural precursor cell expressed developmentally down-regulated gene 4-2, Nedd4-2, is an epilepsy-associated gene with at least three missense mutations identified in epileptic patients. Nedd4-2 encodes a ubiquitin E3 ligase that has high affinity toward binding and ubiquitinating membrane proteins. It is currently unknown how Nedd4-2 mediates neuronal circuit activity and how its dysfunction leads to seizures or epilepsies. In this study, we provide evidence to show that Nedd4-2 mediates neuronal activity and seizure susceptibility through ubiquitination of GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, (AMPAR)...
February 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28211453/mechanism-of-partial-agonism-in-ampa-type-glutamate-receptors
#3
Hector Salazar, Clarissa Eibl, Miriam Chebli, Andrew Plested
Neurotransmitters trigger synaptic currents by activating ligand-gated ion channel receptors. Whereas most neurotransmitters are efficacious agonists, molecules that activate receptors more weakly-partial agonists-also exist. Whether these partial agonists have weak activity because they stabilize less active forms, sustain active states for a lesser fraction of the time or both, remains an open question. Here we describe the crystal structure of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) ligand binding domain (LBD) tetramer in complex with the partial agonist 5-fluorowillardiine (FW)...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28210712/identification-of-an-epidermal-keratinocyte-ampa-glutamate-receptor-involved-in-dermatopathies-associated-with-sensory-abnormalities
#4
David Cabañero, Takeshi Irie, Marta Celorrio, Christopher Trousdale, David M Owens, David Virley, Phillip J Albrecht, Michael J Caterina, Frank L Rice, Jose A Morón
INTRODUCTION: Epidermal keratinocytes are increasingly recognized as active participants in the sensory transduction of itch and pain, processes known to involve primary afferent glutamatergic neurons. However the role of keratinocyte glutamate signaling in sensory functioning is not fully understood. Here, we present the observation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid type glutamate receptors (AMPAR) in epidermal keratinocytes. METHODS: Immunohistochemical and in situ hybridization analyses were conducted to assess the expression of AMPAR subunits in epidermal keratinocytes in mouse and human skin samples, and in organotypic cultures of human keratinocytes...
September 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/28208729/altered-intracellular-milieu-of-adar2-deficient-motor-neurons-in-amyotrophic-lateral-sclerosis
#5
REVIEW
Takenari Yamashita, Megumi Akamatsu, Shin Kwak
Transactive response DNA-binding protein (TDP-43) pathology, and failure of A-to-I conversion (RNA editing) at the glutamine/arginine (Q/R) site of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of most patients with amyotrophic lateral sclerosis (ALS). Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes GluA2 Q/R site-RNA editing. Furthermore, conditional ADAR2 knockout mice (AR2) exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons, which is the most reliable pathological marker of ALS...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28208013/sex-differences-in-autism-like-behavioral-phenotypes-and-postsynaptic-receptors-expression-in-the-prefrontal-cortex-of-tert-transgenic-mice
#6
Ki Chan Kim, Kyu Suk Cho, Sung Min Yang, Edson Luck Gonzales, Schley Valencia, Pyeong Hwa Eun, Chang Soon Choi, Darine Froy Mabunga, Ji-Woon Kim, Judy Kyoungju Noh, Hee Jin Kim, Se Jin Jeon, Seol-Heui Han, Geon Ho Bahn, Chan Young Shin
Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28202907/calpain-1-deletion-impairs-mglur-dependent-ltd-and-fear-memory-extinction
#7
Guoqi Zhu, Victor Briz, Jeff Seinfeld, Yan Liu, Xiaoning Bi, Michel Baudry
Recent studies indicate that calpain-1 is required for the induction of long-term potentiation (LTP) elicited by theta-burst stimulation in field CA1 of hippocampus. Here we determined the contribution of calpain-1 in another type of synaptic plasticity, the long-term depression (LTD) elicited by activation of type-I metabotropic glutamate receptors (mGluR-LTD). mGluR-LTD was associated with calpain-1 activation following T-type calcium channel opening, and resulted in the truncation of a regulatory subunit of PP2A, B56α...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195646/ns1209-spd-502-a-novel-selective-ampa-antagonist-for-stroke-neuropathic-pain-or-epilepsy-drug-development-lessons-learned
#8
Jan M Keppel Hesselink
Preclinical Research The selective AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist, NS1209 (also known as SPD 502) has been explored in several research and development campaigns since its selection as a lead drug candidate in the early 1990s by the Danish biotechnology company, NeuroSearch. The compound was successively tested in animal models of stroke, neuropathic pain and epilepsy. The preclinical data to support development for the treatment of stroke were incomplete, as the compound was administered after the stroke episode, and did not protect subcortical areas of the brain...
February 13, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28195308/ca-2-permeable-ampa-receptors-associated-with-epileptogenesis-of-hypothalamic-hamartoma
#9
Hiroki Kitaura, Masaki Sonoda, Sayaka Teramoto, Hiroshi Shirozu, Hiroshi Shimizu, Tadashi Kimura, Hiroshi Masuda, Yosuke Ito, Hitoshi Takahashi, Shin Kwak, Shigeki Kameyama, Akiyoshi Kakita
Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca(2+) permeability through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues...
February 13, 2017: Epilepsia
https://www.readbyqxmd.com/read/28194001/enhancing-vta-cav1-3-l-type-ca-2-channel-activity-promotes-cocaine-and-mood-related-behaviors-via-overlapping-ampa-receptor-mechanisms-in-the-nucleus-accumbens
#10
A Martínez-Rivera, J Hao, T F Tropea, T P Giordano, M Kosovsky, R C Rice, A Lee, R L Huganir, J Striessnig, N A Addy, S Han, A M Rajadhyaksha
Genetic factors significantly influence susceptibility for substance abuse and mood disorders. Rodent studies have begun to elucidate a role of Cav1.3 L-type Ca(2+) channels in neuropsychiatric-related behaviors, such as addictive and depressive-like behaviors. Human studies have also linked the CACNA1D gene, which codes for the Cav1.3 protein, with bipolar disorder. However, the neurocircuitry and the molecular mechanisms underlying the role of Cav1.3 in neuropsychiatric phenotypes are not well established...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28192396/metabotropic-action-of-postsynaptic-kainate-receptors-triggers-hippocampal-long-term-potentiation
#11
Milos M Petrovic, Silvia Viana da Silva, James P Clement, Ladislav Vyklicky, Christophe Mulle, Inmaculada M González-González, Jeremy M Henley
Long-term potentiation (LTP) in the rat hippocampus is the most extensively studied cellular model for learning and memory. Induction of classical LTP involves an NMDA-receptor- and calcium-dependent increase in functional synaptic AMPA receptors, mediated by enhanced recycling of internalized AMPA receptors back to the postsynaptic membrane. Here we report a physiologically relevant NMDA-receptor-independent mechanism that drives increased AMPA receptor recycling and LTP. This pathway requires the metabotropic action of kainate receptors and activation of G protein, protein kinase C and phospholipase C...
February 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28186680/the-group-ii-metabotropic-glutamate-receptor-agonist-ly354740-and-the-d2-receptor-antagonist-haloperidol-reduce-locomotor-hyperactivity-but-fail-to-rescue-spatial-working-memory-in-glua1-knockout-mice
#12
Thomas Boerner, Alexei Bygrave, Jingkai Chen, Anushka Fernando, Stephanie Jackson, Chris Barkus, Rolf Sprengel, Peter H Seeburg, Paul J Harrison, Gary Gilmour, David M Bannerman, David J Sanderson
Group II metabotropic glutamate receptor agonists have been suggested as potential anti-psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome-wide association studies...
February 10, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28180185/precision-therapy-for-a-new-disorder-of-ampa-receptor-recycling-due-to-mutations-in-atad1
#13
Rebecca C Ahrens-Nicklas, George K E Umanah, Neal Sondheimer, Matthew A Deardorff, Alisha B Wilkens, Laura K Conlin, Avni B Santani, Addie Nesbitt, Jane Juulsola, Erica Ma, Ted M Dawson, Valina L Dawson, Eric D Marsh
OBJECTIVE: ATAD1 encodes Thorase, a mediator of α-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptor recycling; in this work, we characterized the phenotype resulting from ATAD1 mutations and developed a targeted therapy in both mice and humans. METHODS: Using exome sequencing, we identified a novel ATAD1 mutation (p.E276X) as the etiology of a devastating neurologic disorder characterized by hypertonia, seizures, and death in a consanguineous family...
February 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28178527/an-intrinsic-transcriptional-program-underlying-synaptic-scaling-during-activity-suppression
#14
Katie Schaukowitch, Austin L Reese, Seung-Kyoon Kim, Gokhul Kilaru, Jae-Yeol Joo, Ege T Kavalali, Tae-Kyung Kim
Homeostatic scaling allows neurons to maintain stable activity patterns by globally altering their synaptic strength in response to changing activity levels. Suppression of activity by the blocking of action potentials increases synaptic strength through an upregulation of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Although this synaptic upscaling was shown to require transcription, the molecular nature of the intrinsic transcription program underlying this process and its functional significance have been unclear...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28178321/ampa-glua1-flip-targeted-oligonucleotide-therapy-reduces-neonatal-seizures-and-hyperexcitability
#15
Nicole M Lykens, David J Coughlin, Jyoti M Reddi, Gordon J Lutz, Melanie K Tallent
Glutamate-activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs) mediate the majority of excitatory neurotransmission in brain and thus are major drug targets for diseases associated with hyperexcitability or neurotoxicity. Due to the critical nature of AMPA-Rs in normal brain function, typical AMPA-R antagonists have deleterious effects on cognition and motor function, highlighting the need for more precise modulators. A dramatic increase in the flip isoform of alternatively spliced AMPA-R GluA1 subunits occurs post-seizure in humans and animal models...
2017: PloS One
https://www.readbyqxmd.com/read/28176276/maintained-ltp-and-memory-are-lost-by-zn-2-influx-into-dentate-granule-cells-but-not-ca-2-influx
#16
Atsushi Takeda, Haruna Tamano, Marie Hisatsune, Taku Murakami, Hiroyuki Nakada, Hiroaki Fujii
The idea that maintained LTP and memory are lost by either increase in intracellular Zn(2+) in dentate granule cells or increase in intracellular Ca(2+) was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K(+) into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K(+)-induced increase in intracellular Zn(2+) but not high K(+)-induced increase in intracellular Ca(2+). High K(+)-induced disturbances of LTP and intracellular Zn(2+) are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels...
February 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28167075/inhibition-of-the-nmda-and-ampa-receptor-channels-by-antidepressants-and-antipsychotics
#17
Oleg I Barygin, Elina I Nagaeva, Denis B Tikhonov, Darya A Belinskaya, Nina P Vanchakova, Natalia N Shestakova
It is known that some antidepressants and antipsychotics directly inhibit NMDA-type ionotropic glutamate receptors. In this study we systematically studied action of seven drugs (Fluoxetine, Citalopram, Desipramine, Amitriptyline, Atomoxetine, Chlorpromazine, and Clozapine) on NMDA receptors and Ca(2+)-permeable and -impermeable AMPA receptors in rat brain neurons by whole-cell patch-clamp technique. Except for weak effect of fluoxetine, all drugs were virtually inactive against Ca(2+)-impermeable AMPA receptors...
February 3, 2017: Brain Research
https://www.readbyqxmd.com/read/28165451/corrigendum-modulation-of-ampa-receptor-mediated-current-by-nicotinic-acetylcholine-receptor-in-layer-i-neurons-of-rat-prefrontal-cortex
#18
Bo Tang, Dong Luo, Jie Yang, Xiao-Yan Xu, Bing-Lin Zhu, Xue-Feng Wang, Zhen Yan, Guo-Jun Chen
No abstract text is available yet for this article.
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28162513/-276-role-of-ampa-receptor-regulation-in-alcohol-withdrawal-induced-prolongation-of-incisional-pain
#19
S Liu, Y Guo, H Shu, X Yang, F Tao
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28161374/chronic-gabaergic-blockade-in-the-spinal-cord-in%C3%A2-vivo-induces-motor-alterations-and-neurodegeneration
#20
Uri Nimrod Ramírez-Jarquín, Ricardo Tapia
Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord...
February 1, 2017: Neuropharmacology
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