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AMPA receptor

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https://www.readbyqxmd.com/read/28815591/engineering-defined-membrane-embedded-elements-of-ampa-receptor-induces-opposing-gating-modulation-by-cnih3-and-stargazin
#1
Natalie Hawken, Elena Zaika, Terunaga Nakagawa
During excitatory synaptic transmission, various structurally unrelated transmembrane auxiliary subunits control the function of AMPA receptors (AMPARs), but the underlying mechanisms remain unclear. We identified lipid-exposed residues in the transmembrane domain (TMD) of GluA2 subunit of AMPARs that are critical for the function of AMPAR auxiliary subunits, stargazin (Stg) and cornichon 3 (CNIH3). These residues are essential for stabilizing the AMPAR-CNIH3 complex in detergents and overlap with the contacts made between GluA2 TMD and Stg in the cryoEM structures...
August 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28815446/a-human-pet-study-of-11-c-hms011-a-potential-radioligand-for-ampa-receptors
#2
Keisuke Takahata, Yasuyuki Kimura, Chie Seki, Masaki Tokunaga, Masanori Ichise, Kazunori Kawamura, Maiko Ono, Soichiro Kitamura, Manabu Kubota, Sho Moriguchi, Tatsuya Ishii, Yuhei Takado, Fumitoshi Niwa, Hironobu Endo, Tomohisa Nagashima, Yoko Ikoma, Ming-Rong Zhang, Tetsuya Suhara, Makoto Higuchi
BACKGROUND: α-Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor is a primary mediator of fast glutamatergic excitatory signaling in the brain and has been implicated in diverse neuropsychiatric diseases. We recently developed a novel positron emission tomography (PET) ligand, 2-(1-(3-([(11)C]methylamino)phenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl) benzonitrile ([(11)C]HMS011). This compound is a radiolabelled derivative of perampanel, an antiepileptic drug acting on AMPA receptors, and was demonstrated to have promising in vivo properties in the rat and monkey brains...
August 16, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28814784/social-isolation-suppresses-actin-dynamics-and-synaptic-plasticity-through-adf-cofilin-inactivation-in-the-developing-rat-barrel-cortex
#3
Hirobumi Tada, Tomoyuki Miyazaki, Kiwamu Takemoto, Susumu Jitsuki, Waki Nakajima, Mayu Koide, Naoko Yamamoto, Akiko Taguchi, Honami Kawai, Kasane Komiya, Kumiko Suyama, Hiroki Abe, Akane Sano, Takuya Takahashi
Exposure to a stressful environment early in life can cause psychiatric disorders by disrupting circuit formation. Actin plays central roles in regulating neuronal structure and protein trafficking. We have recently reported that neonatal isolation inactivated ADF/cofilin, the actin depolymerizing factor, resulted in a reduced actin dynamics at spines and an attenuation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor delivery in the juvenile rat medial prefrontal cortex (mPFC), leading to altered social behaviours...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814467/input-from-the-medial-geniculate-nucleus-modulates-amygdala-encoding-of-fear-memory-discrimination
#4
Nicole C Ferrara, Patrick K Cullen, Shane P Pullins, Elena K Rotondo, Fred J Helmstetter
Generalization of fear can involve abnormal responding to cues that signal safety and is common in people diagnosed with post-traumatic stress disorder. Differential auditory fear conditioning can be used as a tool to measure changes in fear discrimination and generalization. Most prior work in this area has focused on elevated amygdala activity as a critical component underlying generalization. The amygdala receives input from auditory cortex as well as the medial geniculate nucleus (MgN) of the thalamus, and these synapses undergo plastic changes in response to fear conditioning and are major contributors to the formation of memory related to both safe and threatening cues...
September 2017: Learning & Memory
https://www.readbyqxmd.com/read/28809097/piconewton-scale-analysis-of-ras-braf-signal-transduction-with-single-molecule-force-spectroscopy
#5
Chae-Seok Lim, Cheng Wen, Yanghui Sheng, Guangfu Wang, Zhuan Zhou, Shiqiang Wang, Huaye Zhang, Anpei Ye, J Julius Zhu
Intermolecular interactions dominate the behavior of signal transduction in various physiological and pathological cell processes, yet assessing these interactions remains a challenging task. Here, this study reports a single-molecule force spectroscopic method that enables functional delineation of two interaction sites (≈35 pN and ≈90 pN) between signaling effectors Ras and BRaf in the canonical mitogen-activated protein kinase (MAPK) pathway. This analysis reveals mutations on BRaf at Q257 and A246, two sites frequently linked to cardio-faciocutaneous syndrome, result in ≈10-30 pN alterations in RasBRaf intermolecular binding force...
August 15, 2017: Small
https://www.readbyqxmd.com/read/28808323/stress-hormone-rapidly-tunes-synaptic-nmda-receptor-through-membrane-dynamics-and-mineralocorticoid-signalling
#6
Lenka Mikasova, Hui Xiong, Amber Kerkhofs, Delphine Bouchet, Harm J Krugers, Laurent Groc
Stress hormones, such as corticosteroids, modulate the transmission of hippocampal glutamatergic synapses and NMDA receptor (NMDAR)-dependent synaptic plasticity, favouring salient behavioural responses to the environment. The corticosterone-induced synaptic adaptations partly rely on changes in NMDAR signalling, although the cellular pathway underlying this effect remains elusive. Here, we demonstrate, using single molecule imaging and electrophysiological approaches in hippocampal neurons, that corticosterone specifically controls GluN2B-NMDAR surface dynamics and synaptic content through mineralocorticoid signalling...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#7
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28806920/specific-ion-channels-contribute-to-key-elements-of-pathology-during-secondary-degeneration-following-neurotrauma
#8
Ryan L O'Hare Doig, Wissam Chiha, Marcus K Giacci, Nathanael J Yates, Carole A Bartlett, Nicole M Smith, Stuart I Hodgetts, Alan R Harvey, Melinda Fitzgerald
BACKGROUND: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca(2+) flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes...
August 14, 2017: BMC Neuroscience
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/28804447/activity-dependent-arc-expression-and-homeostatic-synaptic-plasticity-are-altered-in-neurons-from-a-mouse-model-of-angelman-syndrome
#10
Elissa D Pastuzyn, Jason D Shepherd
Angelman syndrome (AS) is a neurodevelopmental disorder that results from deletions or mutations in chromosome 15, which usually includes the UBE3A gene. Ube3A protein is an E3 ubiquitin ligase that ubiquitinates proteins and targets them for degradation. The immediate-early gene Arc, a master regulator of synaptic plasticity, was identified as a putative substrate of Ube3A, but there have been conflicting reports on whether Arc is a bona fide E3 ligase substrate. Using multiple approaches, we found no evidence for a physical interaction between Arc and Ube3A in vivo...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28800112/low-concentration-tributyltin-decreases-glur2-expression-via-nuclear-respiratory-factor-1-inhibition
#11
Keishi Ishida, Kaori Aoki, Tomoko Takishita, Masatsugu Miyara, Shuichiro Sakamoto, Seigo Sanoh, Tomoki Kimura, Yasunari Kanda, Shigeru Ohta, Yaichiro Kotake
Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown...
August 11, 2017: International Journal of Molecular Sciences
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
#12
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/28793258/crucial-roles-for-sirt2-and-ampa-receptor-acetylation-in-synaptic-plasticity-and-memory
#13
Guan Wang, Shaomin Li, James Gilbert, Howard J Gritton, Zemin Wang, Zhangyuan Li, Xue Han, Dennis J Selkoe, Heng-Ye Man
AMPA receptors (AMPARs) mediate fast excitatory synaptic transmission and are crucial for synaptic plasticity, learning, and memory. However, the molecular control of AMPAR stability and its neurophysiological significance remain unclear. Here, we report that AMPARs are subject to lysine acetylation at their C termini. Acetylation reduces AMPAR internalization and degradation, leading to increased cell-surface localization and prolonged receptor half-life. Through competition for the same lysine residues, acetylation intensity is inversely related to the levels of AMPAR ubiquitination...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28780471/neuropathic-pain-attenuating-effects-of-perampanel-in-an-experimental-model-of-chronic-constriction-injury-in-rats
#14
Ravneet Kaur Khangura, Anjana Bali, Gunjanpreet Kaur, Nirmal Singh, Amteshwar Singh Jaggi
The present study explores the pain attenuating effect of perampanel, AMPA receptor antagonist, in chronic constriction injury-induced neuropathic pain. Chronic Constriction Injury was performed by putting four loose ligatures around the sciatic nerve. Pain was assessed by determining mechanical hyperalgesia, cold allodynia and heat hyperalgesia on 7th and 14th day post surgery. Perampanel (3mg and 6mg/kg, p.o.) was administered 30min before pain assessment test on 14th day post-surgery. CCI led to significant development of pain and peak symptoms were observed on 14th day...
August 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28780368/atlanto-occipital-catheterization-of-young-rats-for-long-term-drug-delivery-into-the-lumbar-subarachnoid-space-combined-with-in-vivo-testing-and-electrophysiology-in-situ
#15
Olga Kopach, Volodymyr Krotov, Nana Voitenko
BACKGROUND: Catheterization has been widely used in neuroscience and pain research for local drug delivery. Though different modifications were developed, the use of young animals for spinal catheterization remains limited because of a little success rate. A reliable technique is needed to catheterize young animals aimed for in vivo testing combined with spinal cord electrophysiology, often limited by animal age, to facilitate pain research. NEW METHODS: We describe intrathecal catheterization of young rats (3-week-old) through atlanto-occipical approach for long-lasting drug delivery into the lumbar subarachnoid space...
August 2, 2017: Journal of Neuroscience Methods
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
#16
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/28774570/expression-of-the-glua2-subunit-of-glutamate-receptors-is-required-for-the-normal-dendritic-differentiation-of-cerebellar-purkinje-cells
#17
Masahiko Tanaka, Tomomi Senda, Naohide Hirashima
Cerebellar Purkinje cells differentiate the most elaborate dendritic trees among neurons in the brain and constitute the principal part of cerebellar neuronal circuitry. In the present study, we examined the role of the GluA2 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors in the dendritic differentiation of Purkinje cells. Since mature Purkinje cells express the GluA2 subunit, AMPA receptors on them exhibit a low Ca(2+) permeability. Does this expression of GluA2, leading to the loss of Ca(2+) permeability of AMPA receptors, have a positive significance in the dendritic differentiation of Purkinje cells? To answer this question, we introduced GluA2 siRNA into immature Purkinje cells in cerebellar cell cultures using a single-cell electroporation technique...
July 31, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28769796/s-47445-produces-antidepressant-and-anxiolytic-like-effects-through-neurogenesis-dependent-and-independent-mechanisms
#18
Indira Mendez-David, Jean-Philippe Guilloux, Mariusz Papp, Laurent Tritschler, Elisabeth Mocaer, Alain M Gardier, Sylvie Bretin, Denis J David
Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor's (AMPAR) activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM) possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S 47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT) and in the Chronic Mild Stress (CMS) model in rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28768764/src-homology-2-domain-containing-phosphotyrosine-phosphatase-2-shp2-controls-surface-glua1-in-synaptic-homeostasis
#19
Bin Zhang, Wen Lu
Src Homology 2 Domain Containing Phosphotyrosine Phosphatase 2 (Shp2) functions in synaptic plasticity, learning, and memory. However, the precise mechanisms by which this multifunctional protein contributes to synaptic function remains largely unknown. Homeostatic plasticity may be viewed as a process of bi-directional synaptic scaling, up or down. Through this process neuronal circuitry stability is maintained so that changes in synaptic strength may be preserved under changing conditions. Better understanding of these processes is needed...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28768197/dual-effects-of-tarp-%C3%AE-2-on-glutamate-efficacy-can-account-for-ampa-receptor-autoinactivation
#20
Ian D Coombs, David M MacLean, Vasanthi Jayaraman, Mark Farrant, Stuart G Cull-Candy
Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs) associated with transmembrane AMPAR regulatory proteins (TARPs). At the high glutamate concentrations typically seen during synaptic transmission, TARPs slow receptor desensitization and enhance mean channel conductance. However, their influence on channels gated by low glutamate concentrations, as encountered during delayed transmitter clearance or synaptic spillover, is poorly understood. We report here that TARP γ-2 reduces the ability of low glutamate concentrations to cause AMPAR desensitization and enhances channel gating at low glutamate occupancy...
August 1, 2017: Cell Reports
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