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Glutamate receptors

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https://www.readbyqxmd.com/read/28813782/urea-cycle-pathway-targeted-therapeutic-action-of-naringin-against-ammonium-chloride-induced-hyperammonemic-rats
#1
Arumugam Ramakrishnan, Natesan Vijayakumar
Ammonia is a well-known neurotoxin that causes liver disease and urea cycle disorder. Excessive ammonia content in the blood leads to hyperammonemic condition and affects both excitatory and inhibitory neurotransmission including brain edema and coma. Naringin, a plant bioflavonoid present in various citrus fruits and mainly extracted from the grape fruit. This study was designed to assess the protective effect of naringin on ammonium chloride (NH4Cl) induced hyperammonemic rats. Experimental hyperammonemia was induced by intraperitoneal injections (i...
August 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28811138/intermittent-hypoxia-training-powerful-non-invasive-cerebroprotection-against-ethanol-withdrawal-excitotoxicity
#2
REVIEW
Marianna E Jung, Robert T Mallet
Ethanol intoxication and withdrawal exact a devastating toll on the central nervous system. Abrupt ethanol withdrawal provokes massive release of the excitatory neurotransmitter glutamate, which over-activates its postsynaptic receptors, causing intense Ca(2+) loading, p38 mitogen activated protein kinase activation and oxidative stress, culminating in ATP depletion, mitochondrial injury, amyloid β deposition and neuronal death. Collectively, these mechanisms produce neurocognitive and sensorimotor dysfunction that discourages continued abstinence...
August 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28809097/piconewton-scale-analysis-of-ras-braf-signal-transduction-with-single-molecule-force-spectroscopy
#3
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/28808237/coding-and-small-non-coding-transcriptional-landscape-of-tuberous-sclerosis-complex-cortical-tubers-implications-for-pathophysiology-and-treatment
#4
James D Mills, Anand M Iyer, Jackelien van Scheppingen, Anika Bongaarts, Jasper J Anink, Bart Janssen, Till S Zimmer, Wim G Spliet, Peter C van Rijen, Floor E Jansen, Martha Feucht, Johannes A Hainfellner, Pavel Krsek, Josef Zamecnik, Katarzyna Kotulska, Sergiusz Jozwiak, Anna Jansen, Lieven Lagae, Paolo Curatolo, David J Kwiatkowski, R Jeroen Pasterkamp, Ketharini Senthilkumar, Lars von Oerthel, Marco F Hoekman, Jan A Gorter, Peter B Crino, Angelika Mühlebner, Brendon P Scicluna, Eleonora Aronica
Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). TSC is associated with autism, intellectual disability and severe epilepsy. Cortical tubers are believed to represent the neuropathological substrates of these disabling manifestations in TSC. In the presented study we used high-throughput RNA sequencing in combination with systems-based computational approaches to investigate the complexity of the TSC molecular network...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807780/mgl-1-on-aiy-neurons-translates-starvation-to-reproductive-plasticity-via-neuropeptide-signaling-in-caenorhabditis-elegans
#5
Haelim Jeong, Young-Ki Paik
Reproductive plasticity is the ability of an animal to modulate its reproductive functions in response to environmental changes. For example, Caenorhabditis elegans, a free-living nematode, can adjust the onsets of oogenesis and embryogenesis under harsh environmental conditions, including starvation. However, the molecular mechanisms used to perceive and translate environmental signals into reproductive functional adjustments remain largely uncharacterized. We discovered that in C. elegans, the glutamate receptor homolog MGL-1 initiated reproductive plasticity in response to starvation...
August 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28807676/crf-modulates-glutamate-transmission-in-the-central-amygdala-of-na%C3%A3-ve-and-ethanol-dependent-rats
#6
Florence P Varodayan, Diego Correia, Dean Kirson, Sophia Khom, Christopher S Oleata, George Luu, Paul Schweitzer, Marisa Roberto
Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) is hypothesized to drive the development of alcohol dependence, as it regulates ethanol intake and several anxiogenic behaviors linked to withdrawal. Excitatory glutamatergic neurotransmission contributes to alcohol reinforcement, tolerance and dependence. Therefore, in this study we used in vitro slice electrophysiology to investigate the effects of CRF and its receptor subtype (CRF1 and CRF2) antagonists on both evoked and spontaneous action potential-independent glutamatergic transmission in the CeA of naive and ethanol-dependent Sprague-Dawley rats...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28807674/phenylglycine-analogs-are-inhibitors-of-the-neutral-amino-acid-transporters-asct1-and-asct2-and-enhance-nmda-receptor-mediated-ltp-in-rat-visual-cortex-slices
#7
Alan C Foster, Natalie Rangel-Diaz, Ursula Staubli, Jia-Ying Yang, Mahmud Penjwini, Veena Viswanath, Yong-Xin Li
The N-methyl-d-aspartate receptor (NMDA) co-agonist d-serine is a substrate for the neutral amino acid transporters ASCT1 (SLC1A4) and ASCT2 (SLC1A5). We identified l-phenylglycine (PG) and its analogs as inhibitors of ASCT1 and ASCT2. PG analogs were shown to be non-substrate inhibitors of ASCT1 and ASCT2 with a range of activities relative to other amino acid transport systems, including sodium-dependent glutamate transporters, the sodium-independent d-serine transporter asc-1 and system L. L-4-chloroPG was the most potent and selective ASCT1/2 inhibitor identified...
August 11, 2017: Neuropharmacology
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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