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Glutamate receptor

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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
#1
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/28804557/motor-neuron-degeneration-following-glycine-mediated-excitotoxicity-induces-spastic-paralysis-after-spinal-cord-ischemia-reperfusion-injury-in-rabbit
#2
Li Wang, Sen Li, Yuan Liu, Dong-Liang Feng, Long Jiang, Zai-Yun Long, Ya-Min Wu
Spinal cord ischemia and reperfusion (SCIR) injury is the major cause of a wide range of complications, including neural degeneration and devastating paraplegia. Decrease of inhibitory neurotransmitters and increase of excitory neurotransmitters are the major cause for the excitotoxicity of neurons. However, no study has reported the temporal loss of motor neuron in the ventral horn of spinal cord area following SCIR-induced spastic paralysis, not even the mechanism under it. In the present study, we found that the rabbits were mainly spastic paralyzed after spinal cord ischemia-reperfusion injury...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28802861/contrasting-effects-of-vortioxetine-and-paroxetine-on-pineal-gland-biochemistry-in-a-tryptophan-depletion-model-of-depression-in-female-rats
#3
M Franklin, N Hlavacova, Y Li, I Bermudez, A Csanova, C Sanchez, D Jezova
We studied the effects of the multi-modal antidepressant, vortioxetine and the SSRI, paroxetine on pineal melatonin and monoamine synthesis in a sub-chronic tryptophan (TRP) depletion model of depression based on a low TRP diet. Female Sprague-Dawley rats were randomised to groups a) control, b) low TRP diet, c) low TRP diet+paroxetine and d) low TRP diet+vortioxetine. Vortioxetine was administered via the diet (0.76mg/kg of food weight) and paroxetine via drinking water (10mg/kg/day) for 14days. Both drugs resulted in SERT occupancies >90%...
August 9, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28802219/development-and-validation-of-a-high-performance-liquid-chromatography-tandem-mass-spectrometry-method-to-quantify-ly-354-740-in-rat-and-marmoset-plasma
#4
Fleur Gaudette, Adjia Hamadjida, Dominique Bédard, Stephen G Nuara, Francis Beaudry, Philippe Huot
LY-354,740 (eglumegad) is a selective and potent agonist of the metabotropic glutamate group II receptors (mGluR2,3) that has already entered clinical trials as a potential anti-psychotic agent and therefore has well-documented pharmacokinetic (PK), safety and tolerability profiles in human. Whereas its development as an anti-psychotic agent has not been pursued, LY-354,740 may have potential in other neuroscience-related fields, notably anxiety and neuro-protection. The common marmoset is a small primate that has long been used in neuroscience...
July 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28800512/metabotropic-glutamate-receptors-as-emerging-research-targets-in-bipolar-disorder
#5
REVIEW
Caren J Blacker, Charles P Lewis, Mark A Frye, Marin Veldic
Glutamatergic dysregulation is implicated in the neuropathology of bipolar disorder (BD). There is increasing interest in investigating the role of metabotropic glutamate receptors (mGluRs) in BD and as a target for treatment intervention. Bipolar mGluR studies (published January 1992-April 2016) were identified via PubMed, Embase, Web of Science, and Scopus. Full-text screening, data extraction, and quality appraisal were conducted in duplicate, with strict inclusion and exclusion criteria. The initial literature search for mGluRs in BD, including non-bipolar mood disorders and primary psychotic disorders, identified 1544 articles...
July 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28800112/low-concentration-tributyltin-decreases-glur2-expression-via-nuclear-respiratory-factor-1-inhibition
#6
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/28799954/effects-of-systemic-glutamatergic-manipulations-on-conditioned-eyeblink-responses-and-hyperarousal-in-a-rabbit-model-of-post-traumatic-stress-disorder
#7
Lauren B Burhans, Carrie A Smith-Bell, Bernard G Schreurs
Glutamatergic dysfunction is implicated in many neuropsychiatric conditions, including post-traumatic stress disorder (PTSD). Glutamate antagonists have shown some utility in treating PTSD symptoms, whereas glutamate agonists may facilitate cognitive behavioral therapy outcomes. We have developed an animal model of PTSD, based on conditioning of the rabbit's eyeblink response, that addresses two key features: conditioned responses (CRs) to cues associated with an aversive event and a form of conditioned hyperarousal referred to as conditioning-specific reflex modification (CRM)...
August 9, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28795601/poly-glutamic-dendrimer-based-conjugates-for-cancer-vaccination-a-computational-design-for-targeted-delivery-of-antigens
#8
L I F Moura, N Martinho, L C Silva, T S Barata, S Brocchini, H F Florindo, M Zloh
Computational techniques are useful to predict interaction models and molecular properties for the design of drug delivery systems, such as dendrimers. This work evaluated the impact of surface modifications of mannosamine-conjugated multifunctional poly(glutamic acid) (PG)-dendrimers as nanocarriers of the tumour associated antigens (TAA) MART-1, gp100:44 and gp100:209. Molecular dynamics simulations and docking studies were performed. Nitrobenzoxadiazole (NBD)-PG-G4-dendrimer displayed 64 carboxylic groups, however, the Frontier Molecular Orbital Theory study evidenced that only 32 of those were available to form covalent bonds...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28795439/g-protein-coupled-receptor-37-like-1-modulates-astrocyte-glutamate-transporters-and-neuronal-nmda-receptors-and-is-neuroprotective-in-ischemia
#9
Sarah Jolly, Narges Bazargani, Alejandra C Quiroga, Nigel P Pringle, David Attwell, William D Richardson, Huiliang Li
We show that the G protein-coupled receptor GPR37-like 1 (GPR37L1) is expressed in most astrocytes and some oligodendrocyte precursors in the mouse central nervous system. This contrasts with GPR37, which is mainly in mature oligodendrocytes. Comparison of wild type and Gpr37l1(-/-) mice showed that loss of GPR37L1 did not affect the input resistance or resting potential of astrocytes or neurons in the hippocampus. However, GPR37L1-mediated signalling inhibited astrocyte glutamate transporters and - surprisingly, given its lack of expression in neurons - reduced neuronal NMDA receptor (NMDAR) activity during prolonged activation of the receptors as occurs in ischemia...
August 10, 2017: Glia
https://www.readbyqxmd.com/read/28794459/multiple-excitatory-actions-of-orexins-upon-thalamo-cortical-neurons-in-dorsal-lateral-geniculate-nucleus-implications-for-vision-modulation-by-arousal
#10
Lukasz Chrobok, Katarzyna Palus-Chramiec, Anna Chrzanowska, Mariusz Kepczynski, Marian Henryk Lewandowski
The orexinergic system of the lateral hypothalamus plays a crucial role in maintaining wakefulness and mediating arousal in a circadian time-dependent manner. Due to the extensive connections of orexinergic neurons, both orexins (OXA and OXB) exert mainly excitatory effects upon remote brain areas, including the thalamus. The dorsal lateral geniculate nucleus (DLG) is a relay thalamic centre for the visual system. Its thalamo-cortical (TC) neurons convey photic information from the retina to the primary visual cortex...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791385/sigma-1-receptor-activation-ameliorates-anxiety-like-behavior-through-nr2a-creb-bdnf-signaling-pathway-in-a-rat-model-submitted-to-single-prolonged-stress
#11
Li-Li Ji, Jun-Bo Peng, Chang-Hai Fu, Lei Tong, Zhen-Yu Wang
Accumulating evidence has demonstrated that the σ-1 receptor (σ‑1R) possesses neuroprotective effects and is a potential novel therapeutic target for certain psychiatric diseases, including post‑traumatic stress disorder (PTSD) accompanied with anxiety disorder. It has been reported that σ‑1R agonist treatment could be modulated by the brain‑derived neurotrophic factor (BDNF) signaling pathway. However, it remains unclear whether BDNF and its upstream regulator are mechanistically involved in the therapeutic effect of σ‑1R in PTSD...
August 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790999/immunization-with-recombinant-tcdb-encapsulated-nanocomplex-induces-protection-against-clostridium-difficile-challenge-in-a-mouse-model
#12
Yi-Wen Liu, Yu-Hung Chen, Jenn-Wei Chen, Pei-Jane Tsai, I-Hsiu Huang
Clostridium difficile is considered to be one of the major cause of infectious diarrhea in healthcare systems worldwide. Symptoms of C. difficile infection are caused largely by the production of two cytotoxins: toxin A (TcdA) and toxin B (TcdB). Vaccine development is considered desirable as it would decrease the mounting medical costs and mortality associated with C. difficile infections. Biodegradable nanoparticles composed of poly-γ-glutamic acid (γ-PGA) and chitosan have proven to be a safe and effective antigen delivery system for many viral vaccines...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28790021/deficient-striatal-adaptation-in-aminergic-and-glutamatergic-neurotransmission-is-associated-with-tardive-dyskinesia-in-non-human-primates-exposed-to-antipsychotic-drugs
#13
Catherine Lévesque, Giovanni Hernandez, Souha Mahmoudi, Frédéric Calon, Fabrizio Gasparini, Baltazar Gomez-Mancilla, Pierre J Blanchet, Daniel Lévesque
Tardive dyskinesia (TD) is a potentially disabling condition encompassing all delayed, persistent, and often irreversible abnormal involuntary movements arising in a fraction of subjects during long-term exposure to centrally acting dopamine receptor-blocking agents such as antipsychotic drugs and metoclopramide. However, the pathogenesis of TD has proved complex and remains elusive. To investigate the mechanism underlying the development of TD, we have chronically exposed 17 Cebus apella monkeys to typical (11) or atypical (6) antipsychotic drugs...
August 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28783736/glutamate-alleviates-muscle-protein-loss-by-modulating-tlr4-nods-akt-foxo-and-mtor-signaling-pathways-in-lps-challenged-piglets
#14
Ping Kang, Xiuying Wang, Huanting Wu, Huiling Zhu, Yongqing Hou, Longmei Wang, Yulan Liu
The experiment was conducted to study the effect of the glutamate (Glu) on muscle protein loss through toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain proteins (NODs), Akt/Forkhead Box O (Akt/FOXO) and mammalian target of rapamycin (mTOR) signaling pathways in LPS-challenged piglets. Twenty-four weaned piglets were assigned into four treatments: (1) Control; (2) LPS+0% Glu; (3) LPS + 1.0% Glu; (4) LPS + 2.0% Glu. The experiment was lasted for 28 days. On d 28, the piglets in the LPS challenged groups were injected with LPS on 100 μg/kg body weight (BW), and the piglets in the control group were injected with the same volume of 0...
2017: PloS One
https://www.readbyqxmd.com/read/28782641/nitric-oxide-cgmp-signaling-via-guanylyl-cyclase-isoform-1-modulates-glutamate-and-gaba-release-in-somatosensory-cortex-of-mice
#15
Qi Wang, Evanthia Mergia, Doris Koesling, Thomas Mittmann
In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input-output curves of evoked signals, which indicated the reduction of glutamate and GABA release in NO-GC1 KO mice...
August 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28781167/cross-compartmental-modulation-of-dendritic-signals-for-retinal-direction-selectivity
#16
David Koren, James C R Grove, Wei Wei
Compartmentalized signaling in dendritic subdomains is critical for the function of many central neurons. In the retina, individual dendritic sectors of a starburst amacrine cell (SAC) are preferentially activated by different directions of linear motion, indicating limited signal propagation between the sectors. However, the mechanism that regulates this propagation is poorly understood. Here, we find that metabotropic glutamate receptor 2 (mGluR2) signaling, which acts on voltage-gated calcium channels in SACs, selectively restricts cross-sector signal propagation in SACs, but does not affect local dendritic computation within individual sectors...
July 29, 2017: Neuron
https://www.readbyqxmd.com/read/28780133/altered-glua1-gria1-function-and-accumbal-synaptic-plasticity-in-the-clock%C3%AE-19-model-of-bipolar-mania
#17
Puja K Parekh, Darius Becker-Krail, Poornima Sundaravelu, Shinsuke Ishigaki, Haruo Okado, Gen Sobue, Yanhua Huang, Colleen A McClung
BACKGROUND: Disruptions in circadian rhythms are associated with an increased risk for bipolar disorder. Moreover, studies show that the circadian protein CLOCK (circadian locomotor output cycles kaput) is involved in regulating monoaminergic systems and mood-related behavior. However, the molecular and synaptic mechanisms underlying this relationship remain poorly understood. METHODS: Using ex vivo whole-cell patch-clamp electrophysiology in ClockΔ19 mutant and wild-type mice we characterized alterations in excitatory synaptic transmission, strength, and intrinsic excitability of nucleus accumbens (NAc) neurons...
June 27, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28777881/early-stage-attenuation-of-phase-amplitude-coupling-in-the-hippocampus-and-medial-prefrontal-cortex-in-a-transgenic-rat-model-of-ad
#18
Paolo Bazzigaluppi, Tina L Beckett, Margaret M Koletar, Aaron Y Lai, Illsung L Joo, Mary E Brown, Peter L Carlen, JoAnne McLaurin, Bojana Stefanovic
Alzheimer's disease (AD) is pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ-dependent neuronal dysfunction including modulation of GABAergic signalling. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broad repertoire of AD-like pathologies to investigate the neuronal network functioning using simultaneous intracranial recordings from the hippocampus (HPC) and the medial prefrontal cortex (mPFC), followed by pathological analyses of gamma-aminobutyric acid (GABAA ) receptors subunits α1, α5 and δ, and glutamic acid decarboxylases (GAD65 and GAD67)...
August 4, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28776199/contribution-of-vesicular-glutamate-transporters-to-stress-response-and-related-psychopathologies-studies-in-vglut3-knockout-mice
#19
REVIEW
Hanga Réka Horváth, Csilla Lea Fazekas, Diána Balázsfi, Subodh Kumar Jain, József Haller, Dóra Zelena
Maintenance of the homeostasis in a constantly changing environment is a fundamental process of life. Disturbances of the homeostatic balance is defined as stress response and is induced by wide variety of challenges called stressors. Being the main excitatory neurotransmitter of the central nervous system glutamate is important in the adaptation process of stress regulating both the catecholaminergic system and the hypothalamic-pituitary-adrenocortical axis. Data are accumulating about the role of different glutamatergic receptors at all levels of these axes, but little is known about the contribution of different vesicular glutamate transporters (VGluT1-3) characterizing the glutamatergic neurons...
August 3, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28775326/retrograde-bdnf-to-trkb-signaling-promotes-synapse-elimination-in-the-developing-cerebellum
#20
Myeongjeong Choo, Taisuke Miyazaki, Maya Yamazaki, Meiko Kawamura, Takanobu Nakazawa, Jianling Zhang, Asami Tanimura, Naofumi Uesaka, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano
Elimination of early-formed redundant synapses during postnatal development is essential for functional neural circuit formation. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs). A single CF is strengthened whereas the other CFs are eliminated in each PC dependent on postsynaptic activity in PC, but the underlying mechanisms are largely unknown. Here, we report that brain-derived neurotrophic factor (BDNF) from PC facilitates CF synapse elimination. By PC-specific deletion of BDNF combined with knockdown of BDNF receptors in CF, we show that BDNF acts retrogradely on TrkB in CFs, and facilitates elimination of CF synapses from PC somata during the third postnatal week...
August 4, 2017: Nature Communications
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