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Metabotropic glutamate receptor

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https://www.readbyqxmd.com/read/29147782/common-functional-variants-of-the-glutamatergic-system-in-autism-spectrum-disorder-with-high-and-low-intellectual-abilities
#1
Andreas G Chiocchetti, Afsheen Yousaf, Hannah S Bour, Denise Haslinger, Regina Waltes, Eftichia Duketis, Tomas Jarczok, Michael Sachse, Monica Biscaldi, Franziska Degenhardt, Stefan Herms, Sven Cichon, Jörg Ackermann, Ina Koch, Sabine M Klauck, Christine M Freitag
The genetic architecture underlying Autism spectrum disorder (ASD) has been suggested to differ between individuals with lower (IQ ≤ 70; LIQ) and higher intellectual abilities (IQ > 70; HIQ). Among the identified pathomechanisms, the glutamatergic signalling pathway is of specific interest in ASD. We investigated 187 common functional variants of this neurotransmitter system for association with ASD and with symptom severity in two independent samples, a German (German-ALL: N = 583 families) and the Autism Genome Project cohort (AGP-ALL: N = 2001 families), split into HIQ, and LIQ subgroups...
November 16, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29143330/short-term-high-fat-diet-primes-excitatory-synapses-for-long-term-depression-in-orexin-neurons
#2
Victoria Linehan, Lisa Fang, Michiru Hirasawa
Overconsumption of high-fat diets is one of the strongest contributing factors to the rise of obesity rates. Orexin neurons are known to be activated by palatable high-fat diet and mediate the activation of the mesolimbic reward pathway, resulting in further food intake. While short-term exposure to high-fat diet is known to induce synaptic plasticity within the mesolimbic pathway, it is unknown if such changes occur in orexin neurons. To investigate this, 3-week old male rats were fed a palatable high-fat western diet (WD) or control chow for 1 week and then in vitro patch clamp recording was performed...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29141866/prostate-specific-membrane-antigen-cleavage-of-vitamin-b9-stimulates-oncogenic-signaling-through-metabotropic-glutamate-receptors
#3
Charalambos Kaittanis, Chrysafis Andreou, Haley Hieronymus, Ninghui Mao, Catherine A Foss, Matthias Eiber, Gregor Weirich, Palak Panchal, Anuradha Gopalan, Juan Zurita, Samuel Achilefu, Gabriela Chiosis, Vladimir Ponomarev, Markus Schwaiger, Brett S Carver, Martin G Pomper, Jan Grimm
Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein-coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA's carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29136107/contextual-fear-extinction-induces-hippocampal-metaplasticity-mediated-by-metabotropic-glutamate-receptor-5
#4
Branden J Stansley, Nicole M Fisher, Rocco G Gogliotti, Craig W Lindsley, P Jeffrey Conn, Colleen M Niswender
Dysregulated fear memory can lead to a broad spectrum of anxiety disorders. The brain systems underlying fear memory are manifold, with the hippocampus being prominently involved by housing fear-related spatial memories as engrams, which are created and stored through neural changes such as synaptic plasticity. Although metabotropic glutamate (mGlu) receptors contribute significantly to both fear behavior and hippocampal synaptic plasticity, the relationship between these two phenomena has not been fully elucidated...
November 9, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29117230/two-color-one-photon-uncaging-of-glutamate-and-gaba
#5
Stefan Passlick, Paul F Kramer, Matthew T Richers, John T Williams, Graham C R Ellis-Davies
Neuronal cells receive a variety of excitatory and inhibitory signals which they process to generate an output signal. In order to study the interaction between excitatory and inhibitory receptors with exogenously applied transmitters in the same preparation, two caging chromophores attached to glutamate and GABA were developed that were selectively photolyzed by different wavelengths of light. This technique has the advantage that the biologically inactive caged compound can be applied at equilibrium prior to the near instantaneous release of the transmitters...
2017: PloS One
https://www.readbyqxmd.com/read/29114037/reducing-eif4e-eif4g-interactions-restores-the-balance-between-protein-synthesis-and-actin-dynamics-in-fragile-x-syndrome-model-mice
#6
Emanuela Santini, Thu N Huynh, Francesco Longo, So Yeon Koo, Edward Mojica, Laura D'Andrea, Claudia Bagni, Eric Klann
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism spectrum disorder. FXS is caused by silencing of the FMR1 gene, which encodes fragile X mental retardation protein (FMRP), an mRNA-binding protein that represses the translation of its target mRNAs. One mechanism by which FMRP represses translation is through its association with cytoplasmic FMRP-interacting protein 1 (CYFIP1), which subsequently sequesters and inhibits eukaryotic initiation factor 4E (eIF4E). CYFIP1 shuttles between the FMRP-eIF4E complex and the Rac1-Wave regulatory complex, thereby connecting translational regulation to actin dynamics and dendritic spine morphology, which are dysregulated in FXS model mice that lack FMRP...
November 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/29113156/identification-of-potential-therapeutic-targets-for-gliomas-by-bioinformatics-analysis
#7
Ke Ma, Zhihua Cheng, Liqun Sun, Haibo Li
Gliomas are primary tumors that originate in the brain or spinal cord and develop from supportive glial cells. The present study aimed to identify potential candidate molecular markers for the treatment of gliomas, and to explore the underlying mechanisms of this disease. The gene expression profile data GSE50021, which consisted of 10 specimens of normal brain tissues and 35 specimens of glioma tissues, was downloaded from Gene Expression Omnibus (GEO). The methylation microarray data GSE50022, consisting of 28 glioma specimens, was also downloaded from GEO...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29104538/chronic-treatment-with-fluoxetine-induces-sex-dependent-analgesic-effects-and-modulates-hdac2-and-mglu2-expression-in-female-mice
#8
Magda Zammataro, Sara Merlo, Massimo Barresi, Carmela Parenti, Huijuan Hu, Maria A Sortino, Santina Chiechio
Gender and sex differences in pain recognition and drug responses have been reported in clinical trials and experimental models of pain. Among antidepressants, contradictory results have been observed in patients treated with selective serotonin reuptake inhibitors (SSRIs). This study evaluated sex differences in response to the SSRI fluoxetine after chronic administration in the mouse formalin test. Adult male and female CD1 mice were intraperitoneally injected with fluoxetine (10 mg/kg) for 21 days and subjected to pain assessment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29102027/effect-of-novel-allosteric-modulators-of-metabotropic-glutamate-receptors-on-drug-self-administration-and-relapse-a-review-of-preclinical-studies-and-their-clinical-implications
#9
REVIEW
Daniele Caprioli, Zuzana Justinova, Marco Venniro, Yavin Shaham
Results from preclinical rodent studies during the last 20 years implicated glutamate neurotransmission in different brain regions in drug self-administration and rodent models of relapse. These results, along with evidence for drug-induced neuroadaptations in glutamatergic neurons and receptors, suggested that addiction might be treatable by medications that inhibit glutamatergic responses to drugs of abuse, drug-associated cues, and stressors. This idea is supported by findings in rodent and primate models that drug self-administration and relapse are reduced by systemic injections of antagonists of ionotropic glutamate receptors or metabotropic glutamate receptors (mGluRs) or orthosteric agonists of mGluR2/3...
September 5, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29097780/in-vivo-monitoring-for-regional-changes-of-metabotropic-glutamate-receptor-subtype-1-mglur1-in-pilocarpine-induced-epileptic-rat-brain-by-small-animal-pet
#10
Tomoteru Yamasaki, Masayuki Fujinaga, Wakana Mori, Yiding Zhang, Hidekatsu Wakizaka, Nobuki Nengaki, Lin Xie, Akiko Hatori, Ming-Rong Zhang
Metabotropic glutamate receptor subtype 1 (mGluR1) is a crucial pharmacological target for several central nervous system disorders. In this study, we aimed to monitor in vivo regional changes of mGluR1 related to neuroinflammation in the brains of rats after pilocarpine-induced status epilepticus (PISE) using longitudinal positron emission tomography (PET). PISE was induced in rats by administering lithium chloride, followed by repeated pilocarpine hydrochloride treatments. PET assessments were conducted using N-[4-[6-(isopropylamino)-pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[(11)C]methylbenzamide ([(11)C]ITDM), a selective radioligand for mGluR1, and N-benzyl-N-[(11)C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([(11)C]DAC), a selective translocator protein PET ligand for neuroinflammation monitoring...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29096426/results-and-evaluation-of-a-first-in-human-study-of-rg7342-a-mglu5-positive-allosteric-modulator-utilizing-bayesian-adaptive-methods
#11
Stefan Sturm, Marie-Laure Delporte, Salah Hadi, Scott Schobel, Lothar Lindemann, Robert Weikert, Georg Jaeschke, Michael Derks, Giuseppe Palermo
AIM: The objectives of this first-in-human study were to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, and to determine the maximum tolerated dose (MTD) of single ascending oral doses of RG7342, a positive allosteric modulator (PAM) of the metabotropic glutamate receptor 5 (mGlu5) for the treatment of schizophrenia, in healthy male subjects. METHODS: This was a single-centre, randomized, double-blind, adaptive study of 37 subjects receiving single ascending oral doses of RG7342 (ranging from 0...
November 2, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29079293/functional-partnership-between-mglu3-and-mglu5-metabotropic-glutamate-receptors-in-the-central-nervous-system
#12
Luisa Di Menna, Max E Joffe, Luisa Iacovelli, Rosamaria Orlando, Craig W Lindsley, Jèrome Mairesse, Pierre Gressèns, Milena Cannella, Filippo Caraci, Agata Copani, Valeria Bruno, Giuseppe Battaglia, P Jeffrey Conn, Ferdinando Nicoletti
mGlu5 receptors are involved in mechanisms of activity-dependent synaptic plasticity, and are targeted by drugs developed for the treatment of CNS disorders. We report that mGlu3 receptors, which are traditionally linked to the control of neurotransmitter release, support mGlu5 receptor signaling in neurons and largely contribute to the robust mGlu5 receptor-mediated polyphosphoinositide hydrolysis in the early postnatal life. In cortical pyramidal neurons, mGlu3 receptor activation potentiated mGlu5 receptor-mediated somatic Ca(2+) mobilization, and mGlu3 receptor-mediated long-term depression in the prefrontal cortex required the endogenous activation of mGlu5 receptors...
October 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29074619/presynaptic-mglur5-receptor-controls-glutamatergic-input-through-protein-kinase-c-nmda-receptors-in-paclitaxel-induced-neuropathic-pain
#13
Jing-Dun Xie, Shao-Rui Chen, Hui-Lin Pan
Chemotherapeutic drugs such as paclitaxel cause painful peripheral neuropathy in many cancer patients and survivors. Although NMDA receptors (NMDARs) at primary afferent terminals are known to be critically involved in chemotherapy-induced chronic pain, the upstream signaling mechanism that leads to presynaptic NMDAR activation is unclear. Group I metabotropic glutamate receptors (mGluRs) play a role in synaptic plasticity and NMDAR regulation. Here we report that the Group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) significantly increased the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude of monosynaptic EPSCs evoked from the dorsal root...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29072857/astrocytes-drive-cortical-vasodilatory-signaling-by-activating-endothelial-nmda-receptors
#14
Lingling Lu, Adam D Hogan-Cann, Andrea K Globa, Ping Lu, James I Nagy, Shernaz X Bamji, Christopher M Anderson
Astrocytes express neurotransmitter receptors that serve as sensors of synaptic activity and initiate signals leading to activity-dependent local vasodilation and increases in blood flow. We previously showed that arteriolar vasodilation produced by activation of cortical astrocytes is dependent on endothelial nitric oxide synthase (eNOS) and endogenous agonists of N-methyl-D-aspartate (NMDA) receptors. Here, we tested the hypothesis that these effects are mediated by NMDA receptors expressed by brain endothelial cells...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29071990/-effect-of-electroacupuncture-intervention-on-expression-of-synaptic-plasticity-related-molecules-in-amygdala-in-chronic-pain-negative-affection-rats
#15
Cheng-Lin Duanmu, Xiu-Mei Feng, Ya-Xia Yan, Jun-Ying Wang, Yong-Hui Gao, Li-Na Qiao, Shu-Ping Chen, Jian-Liang Zhang, Jun-Ling Liu
OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of synaptic plasticity-related glutamate N-methyl-D-aspartate (NMDA) receptor subunit NR 1, gamma-aminobutyric acid (GABA) receptor subunits (Aβ 2, B 1), etc. in the amygdala in chronic neuropathic pain negative affection (CNPPNA) rats, so as to reveal its mechanism underlying pain relief. METHODS: Male Wistar rats were randomized into normal control, CNPPNA model, EA, and anesthesia+EA (AEA)groups (n=14 in each group, 8 for quantitative RT-PCR and 6 for immunofluorescence staining)...
February 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29070854/altered-norbin-expression-in-patients-with-epilepsy-and-a-rat-model
#16
Yali Xu, Zengyou Li, Li Yao, Xingping Zhang, Dan Gan, Manchun Jiang, Na Wang, Guojun Chen, Xuefeng Wang
Norbin is widely distributed in neuronal tissues, is a regulator of Ca2(+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation. Norbin is also an important endogenous modulator of metabotropic glutamate receptor 5 (mGluR5) signaling, and nervous system-specific homozygous gene disruptions, result in epileptic seizures. In this study, we aimed to investigate norbin expression patterns in epilepsy and to elucidate the relationships between norbin and mGluR5 and p-CaMKII in epilepsy. Double-immunolabeling, immunohistochemistry and immunoblotting studies showed that norbin was downregulated in the temporal neocortex of patients with temporal lobe epilepsy (TLE) compared with control subjects...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29063113/local-substrates-of-non-receptor-tyrosine-kinases-at-synaptic-sites-in-neurons
#17
Li-Min Mao, Ryan Geosling, Brian Penman, John Q Wang
Several non-receptor tyrosine kinase (nRTK) members are expressed in neurons of mammalian brains. Among these neuron-enriched nRTKs, two Src family kinase members (Src and Fyn) are particularly abundant at synaptic sites and have been most extensively studied for their roles in the regulation of synaptic activity and plasticity. Increasing evidence shows that the synaptic subpool of nRTKs interacts with a number of local substrates, including glutamate receptors (both ionotropic and metabotropic glutamate receptors), postsynaptic scaffold proteins, presynaptic proteins, and synapse-enriched enzymes...
October 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29062097/altered-surface-mglur5-dynamics-provoke-synaptic-nmdar-dysfunction-and-cognitive-defects-in-fmr1-knockout-mice
#18
Elisabetta Aloisi, Katy Le Corf, Julien Dupuis, Pei Zhang, Melanie Ginger, Virginie Labrousse, Michela Spatuzza, Matthias Georg Haberl, Lara Costa, Ryuichi Shigemoto, Anke Tappe-Theodor, Filippo Drago, Pier Vincenzo Piazza, Christophe Mulle, Laurent Groc, Lucia Ciranna, Maria Vincenza Catania, Andreas Frick
Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29055799/altered-mglur5-binding-potential-and-glutamine-concentration-in-the-6-ohda-rat-model-of-acute-parkinson-s-disease-and-levodopa-induced-dyskinesia
#19
Melissa Crabbé, Anke Van der Perren, Akila Weerasekera, Uwe Himmelreich, Veerle Baekelandt, Koen Van Laere, Cindy Casteels
Several lines of evidence point to alterations in glutamatergic signaling in Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), involving the metabotropic glutamate receptor type 5 (mGluR5). Using small-animal positron emission tomography (PET) with [(18)F]FPEB and proton magnetic resonance spectroscopy, we investigated cerebral changes in the mGluR5 and glutamate/glutamine availability in vivo in PD rats and following onset of LIDs. In parallel, behavioral tests were performed. Comparing PD to control rats, mGluR5 binding potential was decreased in a cluster comprising the bilateral caudate-putamen (CP), ipsilateral motor cortex and somatosensory cortex, and the contralateral somatosensory cortex and parietal association cortex, with the most pronounced reduction in the ipsilateral CP...
September 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29054881/ablation-of-tfr1-in-purkinje-cells-inhibits-mglu1-trafficking-and-impairs-motor-coordination-but-not-autistic-like-behaviors
#20
Jia-Huan Zhou, Xin-Tai Wang, Liang Zhou, Lin Zhou, Fang-Xiao Xu, Li-Da Su, Hao Wang, Fan Jia, Fu-Qiang Xu, Gui-Quan Chen, Chris De Zeeuw, Ying Shen
Group 1 metabotropic glutamate receptors (mGlu1/5) are critical to synapse formation and participate in synaptic long-term potentiation (LTP) and long-term depression (LTD) in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a trans-membrane protein of clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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