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https://www.readbyqxmd.com/read/29233883/uncorking-ampa-receptors
#1
Caitlin Sedwick
New JGP study explains how auxiliary proteins relieve polyamine block of AMPARs.
December 12, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29230056/the-c-terminal-tails-of-endogenous-glua1-and-glua2-differentially-contribute-to-hippocampal-synaptic-plasticity-and-learning
#2
Zikai Zhou, An Liu, Shuting Xia, Celeste Leung, Junxia Qi, Yanghong Meng, Wei Xie, Pojeong Park, Graham L Collingridge, Zhengping Jia
Long-term potentiation (LTP) and depression (LTD) at glutamatergic synapses are intensively investigated processes for understanding the synaptic basis for learning and memory, but the underlying molecular mechanisms remain poorly understood. We have made three mouse lines where the C-terminal domains (CTDs) of endogenous AMPA receptors (AMPARs), the principal mediators of fast excitatory synaptic transmission, are specifically exchanged. These mice display profound deficits in synaptic plasticity without any effects on basal synaptic transmission...
December 11, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/29229558/enhanced-activities-of-%C3%AE-subunit-containing-gabaa-receptors-blocked-spinal-long-term-potentiation-and-attenuated-formalin-induced-spontaneous-pain
#3
Jiang-Ping Liu, Yong-Tao He, Xing-Lian Duan, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
The δ subunit-containing γ-Aminobutyric acid type A receptors (δ-GABAARs) are located at extrasynaptic sites and persistently active in the control of neuronal excitability. Here we recorded primary afferent C fiber-evoked field potentials in the superficial dorsal horn of rat spinal cords in vivo, and investigated the possible influence of δ-GABAARs activities on nociceptive synaptic transmission. We found that δ-GABAARs-preferring agonist THIP, when topically applied onto spinal cord dorsum, inhibited the basal synaptic responses in a dose-dependent manner...
December 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29228686/dl-3n-butylphthalide-reduces-epileptiform-activity-through-glua2-lacking-calcium-permeable-ampars-in-epilepsy-models
#4
Qin Yang, Yi-Da Hu, Xue-Feng Wang, Fang-Shuo Zheng
Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epileptic mice, however, the mechanisms are unknown. We investigated behavioral and electrophysiological factors in rats using NBP. In an in vivo pentylenetetrazole (PTZ)-induced epileptic seizure animal model, NBP decreased the generalized tonic-clonic seizure (GTCS) severity...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225271/clinical-relapse-of-anti-ampa-receptor-encephalitis-associated-with-recurrence-of-thymoma
#5
Tsubasa Omi, Makoto Kinoshita, Akira Nishikawa, Takahito Tomioka, Kenichi Ohmori, Kei Fukada, Hidenori Matsunaga
We report a rare case of anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis presenting clinical relapse in association with recurrence of thymoma. Anti-AMPAR encephalitis is an autoimmune-mediated neurological disease, frequently accompanied by the presence of neoplasms, thus comprising the spectrum of paraneoplastic syndrome. A patient had been in remission for 34 months showed clinical relapse 3 months after the detection of recurrent thymoma. Clinical relapse of anti-AMPAR encephalitis after the recurrence of an initially detected neoplasm has not been previously reported...
December 8, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29223596/presence-and-persistence-of-the-amnesic-shellfish-poisoning-toxin-domoic-acid-in-octopus-and-cuttlefish-brains
#6
Vanessa M Lopes, Rui Rosa, Pedro R Costa
Domoic acid (DA) is a neurotoxin that causes degenerative damage to brain cells and induces permanent short-term memory loss in mammals. In cephalopod mollusks, although DA is known to accumulate primarily in the digestive gland, there is no knowledge whether DA reaches their central nervous system. Here we report, for the first time, the presence of DA in brain tissue of the common octopus (Octopus vulgaris) and the European cuttlefish (Sepia officinalis), and its absence in the brains of several squid species (Loligo vulgaris, L...
December 5, 2017: Marine Environmental Research
https://www.readbyqxmd.com/read/29222408/brain-insulin-resistance-impairs-hippocampal-synaptic-plasticity-and-memory-by-increasing-glua1-palmitoylation-through-foxo3a
#7
Matteo Spinelli, Salvatore Fusco, Marco Mainardi, Federico Scala, Francesca Natale, Rosita Lapenta, Andrea Mattera, Marco Rinaudo, Domenica Donatella Li Puma, Cristian Ripoli, Alfonso Grassi, Marcello D'Ascenzo, Claudio Grassi
High-fat diet (HFD) and metabolic diseases cause detrimental effects on hippocampal synaptic plasticity, learning, and memory through molecular mechanisms still poorly understood. Here, we demonstrate that HFD increases palmitic acid deposition in the hippocampus and induces hippocampal insulin resistance leading to FoxO3a-mediated overexpression of the palmitoyltransferase zDHHC3. The excess of palmitic acid along with higher zDHHC3 levels causes hyper-palmitoylation of AMPA glutamate receptor subunit GluA1, hindering its activity-dependent trafficking to the plasma membrane...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29222130/stargazin-and-cornichon-3-relieve-polyamine-block-of-ampa-receptors-by-enhancing-blocker-permeation
#8
Patricia M G E Brown, Hugo McGuire, Derek Bowie
Most ligand- and voltage-gated ion channels assemble as signaling complexes consisting of pore-forming and auxiliary subunits. In the mammalian brain, AMPA-type ionotropic glutamate receptors (AMPARs) coassemble with several families of auxiliary subunits that regulate channel gating as well as ion channel block and permeation. Previous work has shown that auxiliary proteins stargazin (or γ2) and cornichon-3 (CNIH-3) attenuate the cytoplasmic polyamine channel block of AMPARs, although the underlying mechanism has yet to be established...
December 8, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29220673/de-novo-variants-in-gria4-lead-to-intellectual-disability-with-or-without-seizures-and-gait-abnormalities
#9
Sonja Martin, Adam Chamberlin, Deepali N Shinde, Maja Hempel, Tim M Strom, Allison Schreiber, Jessika Johannsen, Lilian Bomme Ousager, Martin J Larsen, Lars Kjaersgaard Hansen, Ali Fatemi, Julie S Cohen, Johannes Lemke, Kristina P Sørensen, Katherine L Helbig, Davor Lessel, Rami Abou Jamra
Using trio whole-exome sequencing, we have identified de novo heterozygous pathogenic variants in GRIA4 in five unrelated individuals with intellectual disability and other symptoms. GRIA4 encodes an AMPA receptor subunit known as GluR4, which is found on excitatory glutamatergic synapses and is important for learning and memory. Four of the variants are located in the highly conserved SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra-cellular domain. Molecular modeling of the altered protein showed that three of the variants in the SYTANLAAF motif orient toward the center of the pore region and most likely lead to disturbance of the gating mechanism...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29218323/sap97-binding-partner-cript-promotes-dendrite-growth-in-vitro-and-in-vivo
#10
Lei Zhang, Angela Marie Jablonski, Jelena Mojsilovic-Petrovic, Hua Ding, Steven Seeholzer, Ian Paterson Newton, Inke Nathke, Rachael Neve, JinBin Zhai, Yuan Shang, Mingjie Zhang, Robert Gordon Kalb
The dendritic tree is a key determinant of neuronal information processing. In the motor system, the dendritic tree of spinal cord neurons undergoes dramatic remodeling in an activity-dependent manner during early postnatal life. This leads to the proper segmental spinal cord connectivity that subserves normal locomotor behavior. One molecular system driving the establishment of dendrite architecture of mammalian motor neurons relies on AMPA receptors (AMPA-Rs) assembled with the GluA1 subunit, and this occurs in an NMDA receptor (NMDA-R)-independent manner...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29216460/getting-a-handle-on-neuropharmacology-by-targeting-receptor-associated-proteins
#11
REVIEW
Michael P Maher, Jose A Matta, Shenyan Gu, Mark Seierstad, David S Bredt
Targeted therapy for neuropsychiatric disorders requires selective modulation of dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically have associated proteins discretely expressed in specific neuronal pathways; these accessory proteins provide a new dimension for drug discovery. Recent studies show that targeting a TARP auxiliary subunit of AMPA receptors selectively modulates neuronal excitability in specific forebrain pathways relevant to epilepsy. Other medicinally important ion channels, gated by glutamate, γ-aminobutyric acid (GABA), and acetylcholine, also have associated proteins, which may be druggable...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29216456/homeostatic-scaling-of-ampa-receptors-by-semaphorin
#12
Amy K Y Fu, Nancy Y Ip
Regulation of AMPA receptors mediates homeostatic scaling. In this issue of Neuron, Wang et al. (2017) identify a new role of secreted semaphorin 3F and elucidate how it triggers synaptic downscaling of AMPA receptors through regulation of the binding of Sema3F holoreceptor complex to AMPA receptors.
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29214650/perampanel-an-ampa-receptor-antagonist-from-clinical-research-to-practice-in-clinical-settings
#13
REVIEW
J-J Tsai, T Wu, H Leung, T Desudchit, S Tiamkao, K-S Lim, A Dash
Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA...
December 7, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/29214210/excitatory-synaptic-input-to-hilar-mossy-cells-under-basal-and-hyperexcitable-conditions
#14
Tristan P Hedrick, William P Nobis, Kendall M Foote, Toshiyuki Ishii, Dane M Chetkovich, Geoffrey T Swanson
Hilar mossy cells (HMCs) in the hippocampus receive glutamatergic input from dentate granule cells (DGCs) via mossy fibers (MFs) and back-projections from CA3 pyramidal neuron collateral axons. Many fundamental features of these excitatory synapses have not been characterized in detail despite their potential relevance to hippocampal cognitive processing and epilepsy-induced adaptations in circuit excitability. In this study, we compared pre- and postsynaptic parameters between MF and CA3 inputs to HMCs in young and adult mice of either sex and determined the relative contributions of the respective excitatory inputs during in vitro and in vivo models of hippocampal hyperexcitability...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29213041/-perampanel-in-the-treatment-of-patients-with-epilepsy
#15
F K Rider
Development of new antiepileptic drugs (AED) does not stop due to the fact that the number of patients with pharmacoresistant epilepsy remains at about 30%. One of the newest AEDs is perampanel (PER), a selective, non-competitive AMPA receptor antagonist to target post-synaptic glutamate transmission. PER is approved in the Russian Federation as adjunctive treatment for focal seizures with or without secondarily generalized seizures and for primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE) in patients with epilepsy aged ≥12 years...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29207398/involvement-of-n-methyl-d-aspartic-acid-receptor-and-dl-%C3%AE-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid-receptor-in-ginsenosides-rb1-and-rb3-against-oxygen-glucose-deprivation-induced-injury-in-hippocampal-slices-from-rat
#16
Shan Jiang, De-Fang Fang, Ying Chen
OBJECTIVE: Ginsenosides, Rb1 and Rb3, are the major protopanaxadiol components of ginseng saponin. In the present study, the influences of ginsenosides Rb1 and Rb3 on N-methyl-D-aspartic acid (NMDA) receptor or DL-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated synaptic transmission after oxygen-glucose deprivation (OGD) were investigated. METHODS: NMDA receptor population spike (NMDA-PS) or AMPA receptor-mediated population spike (AMPA-PS) was recorded in the CA1 pyramidal cell layer of rat hippocampal slices by electrophysiological techniques...
December 5, 2017: Pharmacology
https://www.readbyqxmd.com/read/29204679/gestational-exposure-to-inorganic-arsenic-ias3-alters-glutamate-disposition-in-the-mouse-hippocampus-and-ionotropic-glutamate-receptor-expression-leading-to-memory-impairment
#17
Janikua Nelson-Mora, Martha L Escobar, Luis Rodríguez-Durán, Lourdes Massieu, Teresa Montiel, Verónica M Rodríguez, Karina Hernández-Mercado, María E Gonsebatt
Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have previously observed up-regulation of xCT in the male mouse hippocampus which caused glutamatergic synapse alterations affecting learning and memory processes...
December 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29202853/increased-pkm%C3%AE-activity-impedes-lateral-movement-of-glua2-containing-ampa-receptors
#18
Nam-Kyung Yu, Heesoo Uhm, Jaehoon Shim, Jun-Hyeok Choi, Sangsu Bae, Todd Charlton Sacktor, Sungchul Hohng, Bong-Kiun Kaang
Protein kinase M zeta (PKMζ), a constitutively active, atypical protein kinase C isoform, maintains a high level of expression in the brain after the induction of learning and long-term potentiation (LTP). Further, its overexpression enhances long-term memory and LTP. Thus, multiple lines of evidence suggest a significant role for persistently elevated PKMζ levels in long-term memory. The molecular mechanisms of how synaptic properties are regulated by the increase in PKMζ, however, are still largely unknown...
November 29, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29201361/quercetin-prevents-spinal-motor-neuron-degeneration-induced-by-chronic-excitotoxic-stimulus-by-a-sirtuin-1-dependent-mechanism
#19
Rafael Lazo-Gomez, Ricardo Tapia
Background: Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders. Effective therapeutic strategies are an unmet need for these disorders. Polyphenols, such as quercetin and resveratrol, are plant-derived compounds that activate sirtuins (SIRTs) and have shown promising results in some models of neuronal death, although their effects have been scarcely tested in models of motor neuron degeneration. Methods: In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the rat spinal cord tissue...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29200911/dual-control-of-the-vestibulosympathetic-reflex-following-hypotension-in-rats
#20
Sang Eon Park, Yuan-Zhe Jin, Byung Rim Park
Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP...
November 2017: Korean Journal of Physiology & Pharmacology
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