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Ampa receptors

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https://www.readbyqxmd.com/read/29339535/functional-changes-of-ampa-responses-in-human-induced-pluripotent-stem-cell-derived-neural-progenitors-in-fragile-x-syndrome
#1
Venkat Swaroop Achuta, Tommi Möykkynen, Ulla-Kaisa Peteri, Giorgio Turconi, Claudio Rivera, Kari Keinänen, Maija L Castrén
Altered neuronal network formation and function involving dysregulated excitatory and inhibitory circuits are associated with fragile X syndrome (FXS). We examined functional maturation of the excitatory transmission system in FXS by investigating the response of FXS patient-derived neural progenitor cells to the glutamate analog (AMPA). Neural progenitors derived from induced pluripotent stem cell (iPSC) lines generated from boys with FXS had augmented intracellular Ca2+ responses to AMPA and kainate that were mediated by Ca2+-permeable AMPA receptors (CP-AMPARs) lacking the GluA2 subunit...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29339173/neuroprotective-effects-of-topiramate-and-memantine-in-combination-with-hypothermia-in-hypoxic-ischemic-brain-injury-in-vitro-and-in-vivo
#2
Elisa Landucci, Luca Filippi, Elisabetta Gerace, Serena Catarzi, Renzo Guerrini, Domenico E Pellegrini-Giampietro
Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal mortality and subsequent severe neurological sequelae. Mild hypothermia is a standard therapy for HIE, but is used only in selected Reference Centers and in neonates >1800 g. Since neuronal death following HIE occurs by a cascade of events triggered by activation of glutamate receptors, we used in vitro and in vivo models of HIE to examine whether the AMPA/kainate receptor antagonist topiramate and the NMDA receptor antagonist memantine could exert neuroprotective effects, alone or in combination with hypothermia...
January 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29338492/genetic-variation-of-gria3-gene-is-associated-with-vulnerability-to-methamphetamine-dependence-and-its-associated-psychosis
#3
Sri-Arun Iamjan, Samur Thanoi, Paritat Watiktinkorn, Gavin P Reynolds, Sutisa Nudmamud-Thanoi
Methamphetamine (METH) is an addictive psychostimulant drug commonly leading to schizophrenia-like psychotic symptoms. Disturbances in glutamatergic neurotransmission have been proposed as neurobiological mechanisms and the α-amino-3 hydroxy-5 methyl-4 isoxazole propionic acid (AMPA) glutamate receptor has been implicated in these processes. Moreover, genetic variants in GRIAs, genes encoding AMPA receptor subunits, have been observed in association with both drug dependence and psychosis. We hypothesized that variation of GRIA genes may be associated with METH dependence and METH-induced psychosis...
January 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29337145/interaction-of-dcf1-with-atp1b1-induces-impairment-in-astrocyte-structural-plasticity-via-the-p38-signaling-pathway
#4
Jiao Wang, Fangfang Zhou, Dong Wang, Jie Li, Dongfang Lu, Qian Li, Hong Zhou, Weihao Li, Qian Wang, Yiliu Wu, Jiang Xie, Tieqiao Wen
Astrocytes are known to regulate and support neuronal and synaptic functions. Changes in their size and morphology in mouse models result in mental retardation. However, the mechanism underlying these morphological changes remains unclear. In the present study, abnormal astrocyte morphology was found in the mouse brain following knockout of dendritic cell factor 1 (Dcf1). Immunoprecipitation-mass spectrometry (IP-Mass) identified that ATP1B1 is bound to DCF1, and co-immunoprecipitation and cell fluorescence further confirmed an interaction between these two proteins, with asparagine residue 266 of ATP1B1 being required for the interaction with DCF1...
January 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29335844/the-adiponectin-homolog-osmotin-enhances-neurite-outgrowth-and-synaptic-complexity-via-adipor1-ngr1-signaling-in-alzheimer-s-disease
#5
Gwangho Yoon, Shahid Ali Shah, Tahir Ali, Myeong Ok Kim
Alzheimer's disease is a major neurodegenerative disease characterized by memory loss and cognitive deficits. Recently, we reported that osmotin, which is a homolog of adiponectin, improved long-term potentiation and cognitive functions in Alzheimer's disease mice. Several lines of evidence have suggested that Nogo-A and the Nogo-66 receptor 1 (NgR1), which form a complex that inhibits long-term potentiation and cognitive function, might be associated with the adiponectin receptor 1 (AdipoR1), which is a receptor for osmotin...
January 15, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29330067/protein-complexes-as-psychiatric-and-neurological-drug-targets
#6
REVIEW
Akihiko S Kato, Jeffrey M Witkin
The need for improved medications for psychiatric and neurological disorders is clear. Difficulties in finding such drugs demands that all strategic means be utilized for their invention. The discovery of forebrain specific AMPA receptor antagonists, which selectively block the specific combinations of principal and auxiliary subunits present in forebrain regions but spare targets in the cerebellum, was recently disclosed. This discovery raised the possibility that other auxiliary protein systems could be utilized to help identify new medicines...
January 9, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29330065/stargazin-differentially-modulates-ampakine-gating-kinetics-and-pharmacology
#7
Daniel P Radin, Yong-Xin Li, Gary Rogers, Richard Purcell, Arnold Lippa
It was previously reported that Stargazin (STG) enhances the surface expression of AMPA receptors, controls receptor gating and slows channel desensitization as an auxiliary subunit of the receptors. Ampakines are a class of AMPA receptor positive allosteric modulators that modify rates of transmitter binding, channel activity and desensitization parameters. As such, they have shown efficacy in animal models of neurodegenerative diseases, where excitatory synaptic transmission is compromised. Given the functional similarities between STG and ampakines, the current study sought to probe interactions between STG and ampakine gating properties...
January 9, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29325900/orexin-b-modulates-synaptic-transmission-of-rod-bipolar-cells-in-rat-retina
#8
Gong Zhang, Xiao-Hua Wu, Guo-Zhong Xu, Shi-Jun Weng, Xiong-Li Yang, Yong-Mei Zhong
Orexin-A, -B play a crucial role in arousal and feeding by activating two G-protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Orexins, along with orexin receptors, are expressed in retinal neurons, and they have been shown to differentially modulate excitatory AMPA receptors of amacrine and ganglion cells in the inner retina. In this work we report that orexin-B modulates the activity of rod bipolar cells (RBCs) located in the outer retina of rat. Intravitreal injection of orexin-B increased the amplitude of the scotopic electroretinographic b-wave, a reflection of RBC activity, recorded in vivo...
January 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29325119/mir-96-is-required-for-normal-development-of-the-auditory-hindbrain
#9
Tina Schlüter, Christina Berger, Elena Rosengauer, Pascal Fieth, Constanze Krohs, Kathy Ushakov, Karen P Steel, Karen B Avraham, Alexander Hartmann, Felix Felmy, Hans Gerd Nothwang
The peripheral deafness gene Mir96 is expressed in both the cochlea and central auditory circuits. To investigate whether it plays a role in the auditory system beyond the cochlea, we characterized homozygous Dmdo/Dmdo mice with a point mutation in miR-96. Anatomical analysis demonstrated a significant decrease in volume of auditory nuclei in Dmdo/Dmdo mice. This decrease resulted from decreased cell size. Non-auditory structures in the brainstem of Dmdo/Dmdo mice or auditory nuclei of the congenital deaf Cldn14-/- mice revealed no such differences...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29322377/s-ketamine-current-trends-in-emergency-and-intensive-care-medicine
#10
REVIEW
Helmut Trimmel, Raimund Helbok, Thomas Staudinger, Wolfgang Jaksch, Brigitte Messerer, Herbert Schöchl, Rudolf Likar
S(+)-ketamine, the pure dextrorotatory enantiomer of ketamine has been available for clinical use in analgesia and anesthesia for more than 25 years. The main effects are mediated by non-competitive inhibition of the N-methyl-D-aspartate (NMDA) receptor but S(+)-ketamine also interacts with opioid receptors, monoamine receptors, adenosine receptors and other purinergic receptors. Effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, metabotropic glutamate receptors (mGluR) and L‑type calcium chanels have also been described...
January 10, 2018: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/29317777/a-kinase-anchoring-protein-150-akap150-promotes-cocaine-reinstatement-by-increasing-ampa-receptor-transmission-in-the-accumbens-shell
#11
Leonardo A Guercio, Mackenzie E Hofmann, Sarah E Swinford-Jackson, Julia S Sigman, Mathieu E Wimmer, Mark L Dell'Acqua, Heath D Schmidt, R Christopher Pierce
Previous work indicated that activation of D1-like dopamine receptors (D1DRs) in the nucleus accumbens shell promoted cocaine seeking through a process involving the activation of PKA and GluA1-containing AMPA receptors (AMPARs). A-kinase anchoring proteins (AKAPs) localize PKA to AMPARs leading to enhanced phosphorylation of GluA1. AKAP150, the most well-characterized isoform, plays an important role in several forms of neuronal plasticity. However, its involvement in drug addiction has been minimally explored...
December 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29298820/hbt1-a-novel-ampa-receptor-potentiator-with-lower-agonistic-effect-avoided-bell-shaped-response-in-in-vitro-bdnf-production
#12
Akiyoshi Kunugi, Yasukazu Tajima, Haruhiko Kuno, Satoshi Sogabe, Haruhide Kimura
Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor (AMPA-R) potentiators with brain-derived neurotrophic factor (BDNF)-induction potential could be promising as therapeutic drugs for neuropsychiatric and neurological disorders. However, AMPA-R potentiators such as LY451646 have risks of narrow bell-shaped responses in pharmacological effects, including in vivo BDNF induction. Interestingly, LY451646 and LY451395, other AMPA-R potentiators, showed agonistic effects and exhibited bell-shaped responses in the BDNF production in primary neurons...
January 3, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29289718/a-high-fat-high-sugar-western-diet-alters-dorsal-striatal-glutamate-opioid-and-dopamine-transmission-in-mice
#13
Brandon M Fritz, Braulio Muñoz, Fuqin Yin, Casey Bauchle, Brady K Atwood
Understanding neuroadaptations involved in obesity is critical for developing new approaches to treatment. Diet-induced neuroadaptations within the dorsal striatum have the capacity to drive excessive food seeking and consumption. Five week old C57BL/6J mice consumed a high-fat, high-sugar 'western diet' (WD) or a control 'standard diet' (SD) for 16 weeks. Weight gain, glucose tolerance, and insulin tolerance were measured to confirm an obese-like state. Following these 16 weeks, electrophysiological recordings were made from medium spiny neurons (MSNs) in the medial (DMS) and lateral (DLS) portions of dorsal striatum to evaluate diet effects on neuronal excitability and synaptic plasticity...
December 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/29288725/both-ketamine-and-nbqx-attenuate-alcohol-drinking-in-male-wistar-rats
#14
Jana Ruda-Kucerova, Zuzana Babinska, Matej Luptak, Bruk Getachew, Yousef Tizabi
The devastating consequences of alcohol-use disorder (AUD) on the individual and the society are well established. Current treatments of AUD encompass various strategies, all of which have only modest effectiveness. Hence, there is a critical need to develop more efficacious therapies. Recently, specific glutamatergic receptors have been identified as potential novel targets for intervention in AUD. Thus, the current study was designed to evaluate the effects of acute administration of sub-anesthetic doses of ketamine, an NMDA receptor antagonist, as well as NBQX, an AMPA/kainate receptor antagonist on alcohol intake and its possible behavioural consequences...
December 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29280296/lock-and-chop-a-novel-method-for-the-generation-of-a-pick1-pdz-domain-and-piperidine-based-inhibitor-co-crystal-structure
#15
Douglas J Marcotte, Jean-Christophe Hus, Charles C Banos, Craig Wildes, Robert Arduini, Chris Bergeron, Catherine A Hession, Darren P Baker, Edward Lin, Kevin M Guckian, Anthone W Dunah, Laura F Silvian
The membrane protein interacting with kinase C1 (PICK1) plays a trafficking role in the internalization of neuron receptors such as the amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor. Reduction of surface AMPA type receptors on neurons reduces synaptic communication leading to cognitive impairment in progressive neurodegenerative diseases such as Alzheimer disease. The internalization of AMPA receptors is mediated by the PDZ domain of PICK1 which binds to the GluA2 subunit of AMPA receptors and targets the receptor for internalization through endocytosis, reducing synaptic communication...
December 27, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29277782/oncolytic-properties-of-ampakines-in-vitro
#16
Daniel P Radin, Richard Purcell, Arnold S Lippa
BACKGROUND/AIM: The 5-year survival rate of glioblastoma (GBM) is ~10%, demonstrating that a new therapeutic modality for this cancer is desperately needed. Complicating the search for such a modality is that most large molecules cannot pass through the blood brain barrier, so molecules demonstrating efficacy in vitro may not be useful in vivo because they never reach the brain. Recently, the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) was identified as an effective agent in targeting GBM in vitro and in vivo by agonizing AMPA-glutamate receptors (AMPARs), eliciting massive calcium influx and mitochondrial calcium overload and apoptosis...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29276473/ferric-chelate-reductase-1-like-protein-frrs1l-associates-with-dynein-vesicles-and-regulates-glutamatergic-synaptic-transmission
#17
Wenyan Han, Huiqing Wang, Jun Li, Shizhong Zhang, Wei Lu
In the brain, AMPA receptors (AMPARs)-mediated excitatory synaptic transmission is critically regulated by the receptor auxiliary subunits. Recent proteomic studies have identified that Ferric Chelate Reductase 1 Like protein (FRRS1L), whose mutations in human lead to epilepsy, choreoathetosis, and cognitive deficits, is present in native AMPAR complexes in the brain. Here we have characterized FRRS1L in both heterologous cells and in mouse neurons. We found that FRRS1L interacts with both GluA1 and GluA2 subunits of AMPARs, but does not form dimers/oligomers, in HEK cells...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29274741/a-novel-therapeutic-approach-for-treatment-of-catamenial-epilepsy
#18
Suchitra Joshi, Huayu Sun, Karthik Rajasekaran, John Williamson, Edward Perez-Reyes, Jaideep Kapur
Many women with epilepsy experience perimenstrual seizure exacerbation, referred to as catamenial epilepsy. There is no effective treatment for this condition, proposed to result from withdrawal of neurosteroid-mediated effects of progesterone. A double-blind, multicenter, phase III, clinical trial of catamenial epilepsy has failed to find a beneficial effect of progesterone. The neurosteroid-mediated effects of progesterone have been extensively studied in relation to catamenial epilepsy; however, the effects mediated by progesterone receptor activation have been overlooked...
December 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29262299/atpase-n-ethylmaleimide-sensitive-fusion-protein-a-novel-key-player-for-causing-spontaneous-network-excitation-in-human-temporal-lobe-epilepsy
#19
Christina Herold, Hans-Jürgen Bidmon, Heinz W Pannek, Volkmar Hans, Ali Gorji, Erwin-Josef Speckmann, Karl Zilles
The molecular basis for onset, maintenance and propagation of excitation along neuronal networks in epilepsy is still poorly understood. Beside different neurotransmitter receptors that control signal transfer at the synapse, one key regulator involved in all of these processes is the ATPase N-ethylmaleimide-sensitive fusion protein (NSF). Therefore, we analyzed receptor subunits and NSF levels in tissues from the medial temporal gyrus of patients with pharmaco-resistant focal temporal lobe epilepsy resected during epilepsy surgery and autopsy controls...
December 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/29258299/corrigendum-ampa-receptor-mediated-regulation-of-a-gi-protein-in-cortical-neurons
#20
Yizheng Wang, Daniel L Small, Danica B Stanimirovic, Paul Morley, Jon P Durkin
This corrects the article DOI: 10.1038/39062.
December 20, 2017: Nature
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