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https://www.readbyqxmd.com/read/29790025/ampar-mediated-interictal-discharges-in-neurons-of-entorhinal-cortex-experiment-and-model
#1
A V Chizhov, D V Amakhin, A V Zaizev, L G Magazanik
The mechanisms of interictal discharges (IID) were studied under the conditions of the 4-aminopyridine model of spontaneous epileptiform activity in surviving rat brain slice preparations. Addition of the agents blocking GABA and NMDA receptors failed to inhibit IID generation in the entorhinal cortex. A mathematical model of IID has been developed on the basis of the excitatory neuron interaction mediated by the AMPA receptor. Short-term synaptic depression and slow afterspike-hyperpolarization are the key factors required to terminate a single IID...
March 2018: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/29787770/lateral-hypothalamic-orexin-glucose-inhibited-neurons-may-regulate-reward-based-feeding-by-modulating-glutamate-transmission-in-the-ventral-tegmental-area
#2
Suraj B Teegala, Zhenyu Sheng, Miloni S Dalal, Pamela R Hirschberg, Kevin D Beck, Vanessa H Routh
Glucose inhibits ∼60% of lateral hypothalamic (LH) orexin neurons. Fasting increases the activation of LH orexin glucose-inhibited (GI) neurons in low glucose. Increases in spontaneous glutamate excitatory postsynaptic currents (sEPSCs) onto putative VTA DA neurons in low glucose are orexin dependent (Sheng et al., 2014). VTA DA neurons modulate reward-based feeding (Aston-Jones et al., 2010). We tested the hypothesis that increased activation of LH orexin-GI neurons in low glucose increases glutamate signaling onto VTA DA neurons and contributes to reward-based feeding in food restricted animals...
May 19, 2018: Brain Research
https://www.readbyqxmd.com/read/29784826/deletion-of-lrrtm1-and-lrrtm2-in-adult-mice-impairs-basal-ampa-receptor-transmission-and-ltp-in-hippocampal-ca1-pyramidal-neurons
#3
Mehdi Bhouri, Wade Morishita, Paul Temkin, Debanjan Goswami, Hiroshi Kawabe, Nils Brose, Thomas C Südhof, Ann Marie Craig, Tabrez J Siddiqui, Robert Malenka
Leucine-rich repeat transmembrane (LRRTM) proteins are synaptic cell adhesion molecules that influence synapse formation and function. They are genetically associated with neuropsychiatric disorders, and via their synaptic actions likely regulate the establishment and function of neural circuits in the mammalian brain. Here, we take advantage of the generation of a LRRTM1 and LRRTM2 double conditional knockout mouse ( LRRTM1,2 cKO) to examine the role of LRRTM1,2 at mature excitatory synapses in hippocampal CA1 pyramidal neurons...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29780879/altered-cerebellar-short-term-plasticity-but-no-change-in-postsynaptic-ampa-type-glutamate-receptors-in-a-mouse-model-of-juvenile-batten-disease
#4
Dorota Studniarczyk, Elizabeth L Needham, Hannah M Mitchison, Mark Farrant, Stuart G Cull-Candy
Juvenile Batten disease is the most common progressive neurodegenerative disorder of childhood. It is associated with mutations in the CLN3 gene, causing loss of function of CLN3 protein and degeneration of cerebellar and retinal neurons. It has been proposed that changes in granule cell AMPA-type glutamate receptors (AMPARs) contribute to the cerebellar dysfunction. In this study, we compared AMPAR properties and synaptic transmission in cerebellar granule cells from wild-type and Cln3 knock-out mice. In Cln3 Δ ex1-6 cells, the amplitude of AMPA-evoked whole-cell currents was unchanged...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29777761/functional-organization-of-postsynaptic-glutamate-receptors
#5
REVIEW
Nicky Scheefhals, Harold D MacGillavry
Glutamate receptors are the most abundant excitatory neurotransmitter receptors in the brain, responsible for mediating the vast majority of excitatory transmission in neuronal networks. The AMPA- and NMDA-type ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the fast synaptic responses, while metabotropic glutamate receptors (mGluRs) are coupled to downstream signaling cascades that act on much slower timescales. These functionally distinct receptor sub-types are co-expressed at individual synapses, allowing for the precise temporal modulation of postsynaptic excitability and plasticity...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29775064/enhancing-action-of-positive-allosteric-modulators-through-the-design-of-dimeric-compounds
#6
Thomas Drapier, Pierre Geubelle, Charlotte Bouckaert, Lise Nielsen, Saara Laulumaa, Eric Goffin, Sébastien Dilly, Pierre Francotte, Julien Hanson, Lionel Pochet, Jette Sandholm Kastrup, Bernard Pirotte
The present study describes the identification of highly potent dimeric 1,2,4-benzothiadiazine 1,1-dioxide (BTD)-type positive allosteric modulators of the AMPA receptors (AMPApams) obtained by linking two monomeric BTD scaffolds through their respective 6-positions. Using previous X-ray data from monomeric BTDs co-crystallized with the GluA2o ligand-binding domain (LBD), a molecular modeling approach was performed to predict the preferred dimeric combinations. Two 6,6-ethylene-linked dimeric BTD compounds (16 and 22) were prepared and evaluated as AMPApams on HEK293 cells expressing GluA2o(Q) (calcium flux experiment)...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29774215/importance-of-functional-loss-of-fus-in-ftld-als
#7
REVIEW
Shinsuke Ishigaki, Gen Sobue
Fused in sarcoma (FUS) is an RNA binding protein that regulates RNA metabolism including alternative splicing, transcription, and RNA transportation. FUS is genetically and pathologically involved in frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis (ALS). Multiple lines of evidence across diverse models suggest that functional loss of FUS can lead to neuronal dysfunction and/or neuronal cell death. Loss of FUS in the nucleus can impair alternative splicing and/or transcription, whereas dysfunction of FUS in the cytoplasm, especially in the dendritic spines of neurons, can cause mRNA destabilization...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29771335/loss-of-fragile-x-protein-fmrp-impairs-homeostatic-synaptic-downscaling-through-tumor-suppressor-p53-and-ubiquitin-e3-ligase-nedd4-2
#8
Kwan Young Lee, Kathryn A Jewett, Hee Jung Chung, Nien-Pei Tsai
Synaptic scaling allows neurons to homeostatically readjust synaptic strength upon chronic neural activity perturbations. Although altered synaptic scaling has been implicated to underlie imbalanced brain excitability in neurological disorders such as autism spectrum disorders and epilepsy, the molecular dysregulation and restoration of synaptic scaling in those diseases have not been demonstrated. Here, we showed that the homeostatic synaptic downscaling is absent in the hippocampal neurons of Fmr1 KO mice, the mouse model of the most common inherited autism, Fragile X Syndrome (FXS)...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29770576/the-extracellular-zn-2-concentration-surrounding-excited-neurons-is-high-enough-to-bind-amyloid-%C3%AE-revealed-by-a-nanowire-transistor
#9
Ankur Anand, Chih-Hung Chi, Subhasree Banerjee, Ming-Yi Chou, Fan-Gang Tseng, Chien-Yuan Pan, Yit-Tsong Chen
The Zn2+ stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn2+ concentration (CZn2+ex). This elevation of CZn2+ex regulates the neurotransmission and facilitates the fibrilization of amyloid-β (Aβ). However, the exact CZn2+ex surrounding neurons under (patho)physiological conditions is not clear and the connection between CZn2+ex and the Aβ fibrilization remains obscure. Here, a silicon nanowire field-effect transistor (SiNW-FET) with the Zn2+ -sensitive fluorophore, FluoZin-3 (FZ-3), to quantify the CZn2+ex in real time is modified...
May 16, 2018: Small
https://www.readbyqxmd.com/read/29764453/ampa-ergic-regulation-of-amyloid-%C3%AE-levels-in-an-alzheimer-s-disease-mouse-model
#10
Jane C Hettinger, Hyo Lee, Guojun Bu, David M Holtzman, John R Cirrito
BACKGROUND: Extracellular aggregation of the amyloid-β (Aβ) peptide into toxic multimers is a key event in Alzheimer's disease (AD) pathogenesis. Aβ aggregation is concentration-dependent, with higher concentrations of Aβ much more likely to form toxic species. The processes that regulate extracellular levels of Aβ therefore stand to directly affect AD pathology onset. Studies from our lab and others have demonstrated that synaptic activity is a critical regulator of Aβ production through both presynaptic and postsynaptic mechanisms...
May 15, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29758341/effect-of-zembrin-%C3%A2-and-four-of-its-alkaloid-constituents-on-electric-excitability-of-the-rat-hippocampus
#11
Wilfried Dimpfel, Richard Franklin, Nigel Gericke, Leonie Schombert
ETHNOPHARMACOLOGICAL RELEVANCE: Sceletium tortuosum (Mesembryanthemaceae), a succulent plant indigenous to South Africa. is consumed in the form of teas, decoctions and tinctures and is sometimes smoked and used as snuff. In recent years, Sceletium has received a great deal of commercial interest for relieving stress in healthy people, and for treating a broad range of psychological, psychiatric and inflammatory conditions. MATERIAL AND METHODS: The whole extract (Zembrin®) was tested ex vivo in the hippocampus slice preparation after one week of daily oral administration of 5 and 10mg/kg...
May 11, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29753867/topiramate-mitigates-3-nitropropionic-acid-induced-striatal-neurotoxicity-via-modulation-of-ampa-receptors
#12
Heba N Shalaby, Dalia M El-Tanbouly, Hala F Zaki
Prevalence of glutamate receptor subunit 2 (GluR2)-lacking alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors is a hallmark of excitotoxicity-related neurodegenerative diseases. Topiramate (TPM) is a structurally novel anticonvulsant with a well-known modulatory effects on AMPA/kainate subtypes of glutamate receptors. The present study aimed at investigating the neuroprotective potential of TPM on 3-nitropropionic acid (3-NP)-induced striatal neurodegeneration and Huntington's disease-like symptoms...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29753795/non-anesthetic-effects-of-ketamine-a-review-article-authors-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2
#13
REVIEW
Jabril Eldufani, Alireza Nekoui, Gilbert Blaise
Ketamine is considered a dissociative anesthetic medication, and it is a commonly administered by a parenteral route. It works mainly by blocking the N-methyl-D-aspartate (NMDA) receptor. It inhibits the voltage-gated Na_ and K_ channels and serotonin and dopamine re-uptake; also, it affects specific receptors, such as α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), kainate and aminobutyric acid A receptors. Ketamine appears to have particular mechanisms that are potentially involved during analgesic induction, including enhancing of descending inhibition and anti-inflammatory effects...
May 10, 2018: American Journal of Medicine
https://www.readbyqxmd.com/read/29752691/analytical-modelling-of-temperature-effects-on-an-ampa-type-synapse
#14
Dominik S Kufel, Grzegorz M Wojcik
It was previously reported, that temperature may significantly influence neural dynamics on the different levels of brain function. Thus, in computational neuroscience, it would be useful to make models scalable for a wide range of various brain temperatures. However, lack of experimental data and an absence of temperature-dependent analytical models of synaptic conductance does not allow to include temperature effects at the multi-neuron modeling level. In this paper, we propose a first step to deal with this problem: A new analytical model of AMPA-type synaptic conductance, which is able to incorporate temperature effects in low-frequency stimulations...
May 11, 2018: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/29751228/prenatal-nicotine-exposure-alters-postsynaptic-ampa-receptors-and-glutamate-neurotransmission-within-the-laterodorsal-tegmentum-ldt-of-juvenile-mice
#15
Filip S Polli, Kristi A Kohlmeier
Despite dissemination of information regarding the harm on fetal development of smoking while pregnant, the number of pregnancies associated with nicotine exposure appears to have stagnated. Presence of nicotine during neural formulation is associated with a higher susceptibility of drug dependence, suggesting an altered development of neurons in circuits involved in saliency and motivation. The laterodorsal tegmental nucleus (LDT) plays a role in coding stimuli valence via afferents to mesolimbic nuclei. Accordingly, alterations in development of neural mechanisms in the LDT could be involved in vulnerability to drug dependency...
April 25, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29751227/ampa-receptor-positive-allosteric-modulators-attenuate-morphine-tolerance-and-dependence
#16
Xiaoyu Hu, Xuebi Tian, Xiao Guo, Ying He, Haijun Chen, Jia Zhou, Zaijie Jim Wang
Development of opioid tolerance and dependence hinders the use of opioids for the treatment of chronic pain. In searching for the mechanism and potential intervention for opioid tolerance and dependence, we studied the action of two positive allosteric modulators of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR PAMs). In mice treated with morphine (100 mg/kg, s.c.), acute morphine tolerance and dependence developed in 4-6 h. Treatment with aniracetam, a well-established AMPAR PAM, was able to completely prevent and reverse the development of acute antinociceptive tolerance to morphine...
April 25, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29746395/a-liquid-chromatography-mass-spectrometry-assay-for-determination-of-perampanel-and-concomitant-antiepileptic-drugs-in-the-plasma-of-patients-with-epilepsy-compared-with-a-fluorescent-hplc-assay
#17
Ugo de Grazia, Annachiara D'Urso, Federica Ranzato, Valentina De Riva, Giorgia Contarato, Giuseppe Billo, Francesco Perini, Elisabetta Galloni
BACKGROUND: Perampanel is a novel non-competitive selective antagonist at the postsynaptic ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) glutamate receptor, approved as an adjunctive agent for the treatment of partial-onset seizure with or without secondary generalization and for primary generalized tonic-clonic seizure in patients with epilepsy who are at least 12 years of age. Limited information is available about the clinical utility of therapeutic drug monitoring of perampanel and therapeutic ranges are so far not established...
May 9, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29740596/neuregulin-1-type-i-overexpression-is-associated-with-reduced-nmda-receptor-mediated-synaptic-signaling-in-hippocampal-interneurons-expressing-pv-or-cck
#18
Dimitrios Kotzadimitriou, Wiebke Nissen, Melinda Paizs, Kathryn Newton, Paul J Harrison, Ole Paulsen, Karri Lamsa
Hypofunction of N -methyl-d-aspartate receptors (NMDARs) in inhibitory GABAergic interneurons is implicated in the pathophysiology of schizophrenia (SZ), a heritable disorder with many susceptibility genes. However, it is still unclear how SZ risk genes interfere with NMDAR-mediated synaptic transmission in diverse inhibitory interneuron populations. One putative risk gene is neuregulin 1 ( NRG1 ), which signals via the receptor tyrosine kinase ErbB4, itself a schizophrenia risk gene. The type I isoform of NRG1 shows increased expression in the brain of SZ patients, and ErbB4 is enriched in GABAergic interneurons expressing parvalbumin (PV) or cholecystokinin (CCK)...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29740287/inhibition-of-glur-current-in-microvilli-of-sensory-neurons-via-na-microdomain-coupling-among-glur-hcn-channel-and-na-k-pump
#19
Yasuhiro Kawasaki, Mitsuru Saito, Jonghwa Won, Jin Young Bae, Hajime Sato, Hiroki Toyoda, Eriko Kuramoto, Mikihiko Kogo, Takuma Tanaka, Takeshi Kaneko, Seog Bae Oh, Yong Chul Bae, Youngnam Kang
Glutamatergic dendritic EPSPs evoked in cortical pyramidal neurons are depressed by activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels expressed in dendritic spines. This depression has been attributed to shunting effects of HCN current ( I h ) on input resistance or I h deactivation. Primary sensory neurons in the rat mesencephalic trigeminal nucleus (MTN) have the somata covered by spine-like microvilli that express HCN channels. In rat MTN neurons, we demonstrated that I h enhancement apparently diminished the glutamate receptor (GluR) current ( I GluR ) evoked by puff application of glutamate/AMPA and enhanced a transient outward current following I GluR (OT- I GluR )...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29728964/the-mechanism-of-hyperalgesia-and-anxiety-induced-by-remifentanil-phosphorylation-of-glur1-receptors-in-the-anterior-cingulate-cortex
#20
Jie Zeng, Sisi Li, Chao Zhang, Guijin Huang, Cong Yu
The anterior cingulate cortex (ACC) plays a key role in regulating mood in animals, especially anxiety, and is also a brain region that is indispensable to pain perception. Postoperative anxiety is closely related to the experience of pain. Remifentanil is a commonly used surgical analgesic. The mechanism of supraspinal hyperalgesia caused by remifentanil remains unclear. We used animal models to simulate postoperative hyperalgesia and studied the GluR1 AMPA receptor subunit in the ACC using western blots and immunocytochemistry...
May 4, 2018: Journal of Molecular Neuroscience: MN
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