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Metabotropic glutamate receptor

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https://www.readbyqxmd.com/read/29766042/bc-rna-mislocalization-in-the-fragile-x-premutation
#1
Ilham A Muslimov, Taesun Eom, Anna Iacoangeli, Shih-Chieh Chuang, Renate K Hukema, Rob Willemsen, Dimitre G Stefanov, Robert K S Wong, Henri Tiedge
Fragile X premutation disorder is caused by CGG triplet repeat expansions in the 5' untranslated region of FMR1 mRNA. The question of how expanded CGG repeats cause disease is a subject of continuing debate. Our work indicates that CGG-repeat structures compete with regulatory BC1 RNA for access to RNA transport factor hnRNP A2. As a result, BC1 RNA is mislocalized in vivo, as its synapto-dendritic presence is severely diminished in brains of CGG-repeat knock-in animals (a premutation mouse model). Lack of BC1 RNA is known to cause seizure activity and cognitive dysfunction...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29762713/snap23-kif5-complex-controls-mglu1-receptor-trafficking
#2
Fabrice Raynaud, Vincent Homburger, Martial Seveno, Oana Vigy, Enora Moutin, Laurent Fagni, Julie Perroy
Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 post-synaptic receptor in cultured hippocampal neurons...
May 14, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29762249/numb-p72-but-not-numb-p65-contributes-to-the-trafficking-of-group-i-metabotropic-glutamate-receptors
#3
Na Wang, Xin-Yu Cai, Wei Gao, Ying Shen
The protein Numb localizes to clathrin-coated vesicles and participates in the trafficking of transmembrane receptors. We previous reported that Numb promotes the presence of metabotropic glutamate receptor 1 (mGlu1) on neuronal membrane, and Numb deficiency impairs synaptic expression of mGlu1. However, the actions of different Numb isoforms on mGlu1 trafficking are unknown. Here, we found that Numb-p72 and Numb-p65 are distinctly expressed in HEK293T cells. Interestingly, Numb-p72, but not Numb-p65, binds to mGlu1α and promotes the membrane expression of mGlu1α by antagonizing its internalization...
May 14, 2018: Neuroreport
https://www.readbyqxmd.com/read/29760657/purkinje-cell-signaling-deficits-in-animal-models-of-ataxia
#4
REVIEW
Eriola Hoxha, Ilaria Balbo, Maria Concetta Miniaci, Filippo Tempia
Purkinje cell (PC) dysfunction or degeneration is the most frequent finding in animal models with ataxic symptoms. Mutations affecting intrinsic membrane properties can lead to ataxia by altering the firing rate of PCs or their firing pattern. However, the relationship between specific firing alterations and motor symptoms is not yet clear, and in some cases PC dysfunction precedes the onset of ataxic signs. Moreover, a great variety of ionic and synaptic mechanisms can affect PC signaling, resulting in different features of motor dysfunction...
2018: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29753887/peri-adolescent-drinking-of-ethanol-and-or-nicotine-modulates-astroglial-glutamate-transporters-and-metabotropic-glutamate-receptor-1-in-female-alcohol-preferring-rats
#5
Fawaz Alasmari, Richard L Bell, P S S Rao, Alaa M Hammad, Youssef Sari
Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicated that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression...
May 10, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29753706/improvement-of-impaired-electrical-activity-in-npc1-mutant-cortical-neurons-upon-dhpg-stimulation-detected-by-micro-electrode-array
#6
Xiao Feng, Benjamin M Bader, Fan Yang, Monica Segura, Luise Schultz, Olaf H-U Schröder, Arndt Rolfs, Jiankai Luo
Niemann-Pick Type C1 (NPC1) disease is an autosomal recessive neurodegenerative disease characterized by an excessive accumulation of unesterified cholesterol in late endosomes/lysosomes. Patients with NPC1 disease show a series of symptoms in neuropathology, including a gradually increased loss of motor control and seizures. However, mechanism of the neurological manifestations in NPC1 disease is not fully understood yet. In this study, we utilized the micro-electrode array (MEA) to analyze the spontaneous extracellular electrical activity in cultivated cortical neurons of the NPC1 mutant (NPC1-/- ) mouse...
May 10, 2018: Brain Research
https://www.readbyqxmd.com/read/29753415/early-effects-of-16-o-radiation-on-neuronal-morphology-and-cognition-in-a-murine-model
#7
Hannah Carr, Tyler C Alexander, Thomas Groves, Frederico Kiffer, Jing Wang, Elvin Price, Marjan Boerma, Antiño R Allen
Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory...
May 2018: Life Sciences in Space Research
https://www.readbyqxmd.com/read/29753314/allosteric-and-orthosteric-activators-of-mglur8-differentially-affect-the-chemotherapeutic-induced-human-neuroblastoma-sh-sy5y-cell-damage-the-impact-of-cell-differentiation-state
#8
Danuta Jantas, Beata Grygier, Justyna Zatorska, Władysław Lasoń
The participation of group III metabotropic glutamate receptors (mGluRs) in cancer growth and progression is still an understudied issue. Based on our recent data on high expression of mGluR8 in human neuroblastoma SH-SY5Y cells, in the present study we evaluated the effect of an mGluR8-specific positive allosteric modulator (PAM: AZ12216052) and orthosteric agonist ((S)-3,4-DCPG) on chemotherapeutic (doxorubicin, irinotecan or cisplatin)-evoked cell damage in undifferentiated (UN-) and retinoic acid-differentiated (RA-) SH-SY5Y cells...
May 12, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29751975/editorial-overview-neurosciences-metabotropic-glutamate-receptors-still-promising-drug-targets-for-cns-disorders
#9
EDITORIAL
Ferdinando Nicoletti, Giuseppe Battaglia, Valria Bruno
No abstract text is available yet for this article.
February 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29748927/perinatal-exposure-to-arsenic-in-drinking-water-alters-glutamatergic-neurotransmission-in-the-striatum-of-c57bl-6-mice
#10
Kyunghwa Sung, Minjeong Kim, Haesoo Kim, Gi-Wook Hwang, Kisok Kim
Although exposure to arsenic (As) induces developmental neurotoxicity, there is a lack of data regarding its specific effects on glutamatergic neurotransmission in offspring from dams exposed to As during gestation and lactation. In this study, the body weight, glutamate content, and expression of vesicular glutamate transporter 2 (VGLUT2) and metabotropic glutamate receptors mGluR2 and mGluR3 was examined in the striatum of offspring following treatment of the dams with As (10 or 100 mg/L NaAsO2 in drinking water)...
May 10, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29738887/transcriptome-analysis-reveals-enrichment-of-genes-associated-with-auditory-system-in-swimbladder-of-channel-catfish
#11
Yujia Yang, Xiaozhu Wang, Yang Liu, Qiang Fu, Changxu Tian, Chenglong Wu, Huitong Shi, Zihao Yuan, Suxu Tan, Shikai Liu, Dongya Gao, Rex Dunham, Zhanjiang Liu
In aquatic organisms, hearing is an important sense for acoustic communications and detection of sound-emitting predators and prey. Channel catfish is a dominant aquaculture species in the United States. As channel catfish can hear sounds of relatively high frequency, it serves as a good model for study auditory mechanisms. In catfishes, Weberian ossicles connect the swimbladder to the inner ear to transfer the forced vibrations and improve hearing ability. In this study, we examined the transcriptional profiles of channel catfish swimbladder and other four tissues (gill, liver, skin, and intestine)...
April 30, 2018: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/29738849/5-ht-1a-receptor-stimulation-in-the-medial-prefrontal-cortex-mediates-the-antidepressant-effects-of-mglu2-3-receptor-antagonist-in-mice
#12
Kenichi Fukumoto, Michihiko Iijima, Takeo Funakoshi, Shigeyuki Chaki
We previously reported that serotonergic transmission is involved in the antidepressant effects of metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists. However, the detailed underlying mechanisms had not yet been explored. In the present study, we investigated the role of the 5-HT1A receptor and its signaling cascade in the medial prefrontal cortex (mPFC) in the antidepressant effects of LY341495, an mGlu2/3 receptor antagonist. LY341495 significantly reduced the immobility time in the forced swimming test which sustained for 24 h after administration...
May 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29731708/non-canonical-mechanisms-of-presynaptic-kainate-receptors-controlling-glutamate-release
#13
REVIEW
José V Negrete-Díaz, Talvinder S Sihra, Gonzalo Flores, Antonio Rodríguez-Moreno
A metabotropic modus operandi for kainate receptors (KARs) was first discovered in 1998 modulating GABA release. These receptors have been also found to modulate glutamate release at different synapses in several brain regions. Mechanistically, a general biphasic mechanism for modulating glutamate release by presynaptic KARs with metabotropic actions has emerged, with low KA concentrations invoking an increase in glutamate release, whereas higher concentrations of KA mediate a decrease in the release of this neurotransmitter...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29705142/discovery-of-6-pyrimidin-5-ylmethyl-quinoline-8-carboxamide-negative-allosteric-modulators-of-metabotropic-glutamate-receptor-subtype-5
#14
Andrew S Felts, Alice L Rodriguez, Ryan D Morrison, Anna L Blobaum, Frank W Byers, J Scott Daniels, Colleen M Niswender, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte
Based on previous work that established fused heterocycles as viable alternatives for the picolinamide core of our lead series of mGlu5 negative allosteric modulators (NAMs), we designed a novel series of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide mGlu5 NAMs. These new quinoline derivatives also contained carbon linkers as replacements for the diaryl ether oxygen atom common to our previously published chemotypes. Compounds were evaluated in a cell-based functional mGlu5 assay, and an exemplar analog 27 was >60-fold selective versus the other seven mGlu receptors...
April 22, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29703767/encephalitis-with-mglur5-antibodies-symptoms-and-antibody-effects
#15
Marianna Spatola, Lidia Sabater, Jesús Planagumà, Eugenia Martínez-Hernandez, Thaís Armangué, Harald Prüss, Takahiro Iizuka, Ruben L Caparó Oblitas, Jean-Christophe Antoine, Richard Li, Nicholas Heaney, Niall Tubridy, Elvira Munteis Olivas, Myrna R Rosenfeld, Francesc Graus, Josep Dalmau
OBJECTIVE: To report the clinical features of 11 patients with metabotropic glutamate receptor 5 (mGluR5) antibody-associated encephalitis, immunoglobulin G (IgG) subclass, and effects of the antibodies on neuronal mGluR5 clusters. METHODS: Clinical information was retrospectively obtained from referring physicians. Antibodies to mGluR5 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays. The effects of the antibodies were examined on rat hippocampal neurons with reported techniques...
April 27, 2018: Neurology
https://www.readbyqxmd.com/read/29689337/gender-specific-desensitization-of-group-i-metabotropic-glutamate-receptors-after-maternal-l-glutamate-intake-during-lactation
#16
Antonio López-Zapata, David Agustín León-Navarro, María Crespo, Mairena Martín
In the present work we have studied the effect of maternal intake of l-Glutamate (l-Glu) (1 g/L) during lactation on group I mGluR transduction pathway in brain plasma membrane from 15 days-old neonates. Results obtained have shown that maternal l-glutamate intake did not significantly affect neither weights of pups nor negative geotaxis reflex, an index of neurobehavioral development, but increased l-Glu plasma level in both male and female neonates. In male neonates, maternal l-Glu intake evoked a loss of mGluR1 whereas no variation on mGluR5 was observed as revealed by Western-blotting assay...
April 21, 2018: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29686062/synaptic-adhesion-protein-elfn1-is-a-selective-allosteric-modulator-of-group-iii-metabotropic-glutamate-receptors-in-trans
#17
Henry A Dunn, Dipak N Patil, Yan Cao, Cesare Orlandi, Kirill A Martemyanov
Functional characterization of the GPCR interactome has been focused predominantly on intracellular interactions, yet GPCRs are increasingly found in complex with extracellular proteins. Extracellular leucine-rich repeat fibronectin type III domain containing 1 (ELFN1) was recently reported to physically anchor mGluR6 and mGluR7 across retinal and hippocampal synapses, respectively; however, the consequence of transsynaptic interactions on properties and pharmacology of these receptors are unknown. In the current study, we explore the effects of ELFN1 on mGluR signaling and pharmacology...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29685291/long-term-clinical-follow-up-of-a-patient-with-non-paraneoplastic-cerebellar-ataxia-associated-with-anti-mglur1-autoantibodies
#18
Nobuaki Yoshikura, Akio Kimura, Masaki Fukata, Yuko Fukata, Norihiko Yokoi, Naoko Harada, Yuichi Hayashi, Takashi Inuzuka, Takayoshi Shimohata
The clinical features of cerebellar ataxia associated with anti-metabotropic glutamate receptor 1 (mGluR1) autoantibodies, a rare autoimmune-mediated cerebellar ataxia, remain to be elucidated. Here, we describe a patient with non-paraneoplastic cerebellar ataxia associated with anti-mGluR1 autoantibodies, who was followed up over 5 years. She presented with relapses and remissions of subacute progressive cerebellar ataxia that were responsive to immunotherapy. Although serum anti-mGluR1 autoantibodies were continuously detected and cerebellar atrophy gradually progressed, repeated intravenous immunoglobulin therapy and oral immunosuppressants ensured cerebellar ataxia remained at almost the same level during the observation period...
June 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29682799/the-differences-between-glun2a-and-glun2b-signaling-in-the-brain
#19
REVIEW
Yongjun Sun, Yingge Xu, Xiaokun Cheng, Xi Chen, Yinghua Xie, Linan Zhang, Long Wang, Jie Hu, Zibin Gao
The N-methyl-d-aspartate (NMDA) receptor, a typical ionotropic glutamate receptor, is a crucial protein for maintaining brain function. GluN2A and GluN2B are the main types of NMDA receptor subunit in the adult forebrain. Studies have demonstrated that they play different roles in a number of pathophysiological processes. Although the underlying mechanism for this has not been clarified, the most fundamental reason may be the differences between the signaling pathways associated with GluN2A and GluN2B. With the aim of elucidating the reasons behind the diverse roles of these two subunits, we described the signaling differences between GluN2A and GluN2B from the aspects of C-terminus-associated molecules, effects on typical downstream signaling proteins, and metabotropic signaling...
April 22, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29674969/-in-vitro-functional-characterization-of-get73-as-possible-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-5
#20
Sarah Beggiato, Andrea C Borelli, Maria C Tomasini, M Paola Castelli, Nicholas Pintori, Roberto Cacciaglia, Antonella Loche, Luca Ferraro
The present study was aimed to further characterize the pharmacological profile of N-[4-(trifluoromethyl) benzyl]-4-methoxybutyramide (GET73), a putative negative allosteric modulator (NAM) of metabotropic glutamate subtype 5 receptor (mGluR5) under development as a novel medication for the treatment of alcohol dependence. This aim has been accomplished by means of a series of in vitro functional assays. These assays include the measure of several down-stream signaling [intracellular Ca++ levels, inositol phosphate (IP) formation and CREB phosphorylation (pCREB)] which are generally affected by mGluR5 ligands...
2018: Frontiers in Pharmacology
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