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https://www.readbyqxmd.com/read/29703767/encephalitis-with-mglur5-antibodies-symptoms-and-antibody-effects
#1
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
#2
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/29674969/-in-vitro-functional-characterization-of-get73-as-possible-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-5
#3
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
https://www.readbyqxmd.com/read/29625424/mglu-receptors-in-the-treatment-of-parkinson-s-disease-and-l-dopa-induced-dyskinesia
#4
REVIEW
Irene Sebastianutto, Maria Angela Cenci
Parkinson's disease (PD) is a neurodegenerative disorder characterized by typical motor features that result from dopamine (DA) depletion in the striatum. DA replacement therapy with L-DOPA is the most efficacious symptomatic treatment, but causes complications that limit its utility, in particular, L-DOPA-induced dyskinesia (LID). LID is primarily caused by pre-synaptic and post-synaptic changes in DA neurotransmission, although it also depends on altered glutamatergic transmission at several nodes of the cortico-basal ganglia-thalamocortical network...
April 3, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29614089/hippocampal-protein-kinase-d1-is-necessary-for-dhpg-induced-learning-and-memory-impairments-in-rats
#5
Wei Wang, Florian Duclot, Bradley R Groveman, Nicole Carrier, Haifa Qiao, Xiao-Qian Fang, Hui Wang, Wenkuan Xin, Xing-Hong Jiang, Michael W Salter, Xin-Sheng Ding, Mohamed Kabbaj, Xian-Min Yu
BACKGROUND: Understanding molecular mechanisms underlying the induction of learning and memory impairments remains a challenge. Recent investigations have shown that the activation of group I mGluRs (mGluR1 and mGluR5) in cultured hippocampal neurons by application of (S)-3,5-Dihydroxyphenylglycine (DHPG) causes the regulated internalization of N-methyl-D-aspartate receptors (NMDARs), which subsequently activates protein kinase D1 (PKD1). Through phosphorylating the C-terminals of the NMDAR GluN2 subunits, PKD1 down-regulates the activity of remaining (non-internalized) surface NMDARs...
2018: PloS One
https://www.readbyqxmd.com/read/29608920/the-metabotropic-glutamate-receptor-5-radioligand-11-c-azd9272-identifies-unique-binding-sites-in-primate-brain
#6
Katarina Varnäs, Anders Juréus, Sjoerd J Finnema, Peter Johnström, Patrick Raboisson, Nahid Amini, Akihiro Takano, Vladimir Stepanov, Christer Halldin, Lars Farde
The metabotropic glutamate receptor 5 (mGluR5) is a target for drug development and for imaging studies of the glutamate system in neurological and psychiatric disorders. [11 C]AZD9272 is a selective mGluR5 PET radioligand that is structurally different from hitherto applied mGluR5 radioligands. In the present investigation we compared the binding patterns of radiolabeled AZD9272 and other mGluR5 radioligands in the non-human primate (NHP) brain. PET studies were undertaken using [11 C]AZD9272 and the commonly applied mGluR5 radioligand [11 C]ABP688...
March 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29524437/metabotropic-glutamate-receptor-modulation-of-dopamine-release-in-the-nucleus-accumbens-shell-is-unaffected-by-phencyclidine-pretreatment-in-vitro-assessment-using-fast-scan-cyclic-voltammetry-rat-brain-slices
#7
Ishan Gupta, Andrew M J Young
The non-competitive glutamate antagonist, phencyclidine is used in rodents to model behavioural deficits see in schizophrenia. Importantly, these deficits endure long after the cessation of short-term chronic treatment (sub-chronic), indicating that the drug treatment causes long-term changes in the physiology and/or chemistry of the brain. There is evidence that this may occur through glutamatergic modulation of mesolimbic dopamine release, perhaps involving metabotropic glutamate receptors (mGluR). This study sought to investigate the effect of sub-chronic phencyclidine pretreatment on modulation of dopamine neurotransmission by metabotropic glutamate receptors 2 and 5 (mGluR2 and mGluR5) in the nucleus accumbens shell in vitro, with the hypothesis that phencyclidine pretreatment would disrupt the mGluR-mediated modulation of dopamine release...
May 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29496988/glutamatergic-biomarkers-for-cocaine-addiction-a-longitudinal-study-in-self-administering-rats-using-mrs-and-mglur5-pet
#8
Bart de Laat, Akila Weerasekera, Gil Leurquin-Sterk, Guy M Bormans, Uwe Himmelreich, Cindy Casteels, Koen Van Laere
Cocaine addiction is a disorder without diagnostic biomarkers or effective pharmacotherapy. Research on the glutamatergic system lacks longitudinal data starting before exposure to cocaine. We present findings in a rat model of cocaine self-administration that was followed-up longitudinally using the mGluR5 tracer 18 F-FPEB PET, 1H-MRS and behavioral tests. Methods: Forty-two Wistar rats were scanned with 18 F-FPEB PET and 1H-MRS before and after sucrose or IV cocaine self-administration, during withdrawal and relapse...
March 1, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29487381/mglur5-antagonism-inhibits-cocaine-reinforcement-and-relapse-by-elevation-of-extracellular-glutamate-in-the-nucleus-accumbens-via-a-cb1-receptor-mechanism
#9
Xia Li, Xiao-Qing Peng, Chloe J Jordan, Jie Li, Guo-Hua Bi, Yi He, Hong-Ju Yang, Hai-Ying Zhang, Eliot L Gardner, Zheng-Xiong Xi
Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) dose-dependently reduced cocaine (and sucrose) self-administration and cocaine-induced reinstatement of drug-seeking behavior...
February 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29481317/a-postmortem-analysis-of-nmda-ionotropic-and-group-1-metabotropic-glutamate-receptors-in-the-nucleus-accumbens-in-schizophrenia
#10
Jeremy S Lum, Samuel J Millard, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
BACKGROUND: The nucleus accumbens (NAcc) has been implicated in the pathology and treatment of schizophrenia. Recent postmortem evidence suggests a hyperglutamatergic state in the NAcc. With the present study we aimed to explore possible glutamatergic alterations in the NAcc of a large schizophrenia cohort. METHODS: We performed immunoblots on postmortem NAcc samples from 30 individuals who had schizophrenia and 30 matched controls. We examined the protein expression of primary glutamatergic receptors, including the N -methyl-D-aspartate (NMDA) receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate receptor (mGluR1 and mGluR5; dimeric and monomeric forms)...
March 2018: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29467608/understanding-the-role-of-adenosine-a2ar-heteroreceptor-complexes-in-neurodegeneration-and-neuroinflammation
#11
Dasiel O Borroto-Escuela, Sonja Hinz, Gemma Navarro, Rafael Franco, Christa E Müller, Kjell Fuxe
Adenosine is a nucleoside mainly formed by degradation of ATP, located intracellularly or extracellularly, and acts as a neuromodulator. It operates as a volume transmission signal through diffusion and flow in the extracellular space to modulate the activity of both glial cells and neurons. The effects of adenosine are mediated via four adenosine receptor subtypes: A1R, A2AR, A2BR, A3R. The A2AR has a wide-spread distribution but it is especially enriched in the ventral and dorsal striatum where it is mainly located in the striato-pallidal GABA neurons at a synaptic and extrasynaptic location...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29466733/a%C3%A3-facilitates-ltd-at-schaffer-collateral-synapses-preferentially-in-the-left-hippocampus
#12
Kenneth J O'Riordan, Neng-Wei Hu, Michael J Rowan
Promotion of long-term depression (LTD) mechanisms by synaptotoxic soluble oligomers of amyloid-β (Aß) has been proposed to underlie synaptic dysfunction in Alzheimer's disease (AD). Previously, LTD was induced by relatively non-specific electrical stimulation. Exploiting optogenetics, we studied LTD using a more physiologically diffuse spatial pattern of selective pathway activation in the rat hippocampus in vivo. This relatively sparse synaptic LTD requires both the ion channel function and GluN2B subunit of the NMDA receptor but, in contrast to electrically induced LTD, is not facilitated by boosting endogenous muscarinic acetylcholine or metabotropic glutamate 5 receptor activation...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29449954/metabotropic-glutamate-receptor-5-tracer-18-f-fpeb-displays-increased-binding-potential-in-postcentral-gyrus-and-cerebellum-of-male-individuals-with-autism-a-pilot-pet-study
#13
S Hossein Fatemi, Dean F Wong, James R Brašić, Hiroto Kuwabara, Anil Mathur, Timothy D Folsom, Suma Jacob, George M Realmuto, José V Pardo, Susanne Lee
Background: Autism is a neurodevelopmental disorder that is first manifested during early childhood. Postmortem experiments have identified significantly elevated expression of metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and prefrontal cortex of individuals with autism. Methods: In the current study we employed the mGluR5 tracer [18 F]-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([18 F]-FPEB) to quantify mGluR5 binding in vivo in adults with autism vs...
2018: Cerebellum & Ataxias
https://www.readbyqxmd.com/read/29438802/endocannabinoid-signaling-in-embryonic-neuronal-motility-and-cell-cell-contact-role-of-mglur5-and-trpc3-channels
#14
Pauli M Turunen, Lauri M Louhivuori, Verna Louhivuori, Jyrki P Kukkonen, Karl E Åkerman
Cell-cell communication plays a central role in the guidance of migrating neuronal precursor cells during the development of the cerebral cortex. Endocannabinoids (eCBs) have previously been shown to be one of the central factors regulating neuronal migration. In this study the effects of eCBs on different parameters, expected to affect embryonic cortical neuronal motility have been analyzed in neurosphere-derived neuroblasts using time-lapse microscopy. Increased endogenous production of the endocannabinoid 2-arachidonyl glycerol (2-AG) causes bursts of neuroblast motility...
April 1, 2018: Neuroscience
https://www.readbyqxmd.com/read/29427650/a%C3%AE-pathology-downregulates-brain-mglur5-density-in-a-mouse-model-of-alzheimer
#15
Minkyung Lee, Hae-June Lee, In Suh Park, Ji-Ae Park, Yeon Ju Kwon, Young Hoon Ryu, Chul Hoon Kim, Joo Hyun Kang, In Young Hyun, Kyo Chul Lee, Jae Yong Choi
The aim of the present study was to evaluate functional changes of mGluR5 expression in advanced Alzheimer's disease (AD) using positron emission tomography (PET) with an mGluR5 specific radiotracer ([18 F]FPEB) in 5xFAD AD model. Subsequently, in the same animal, mGluR5 expression was quantified by immunoassay techniques. The non-displaceable binding potential values for mGluR5 was estimated by the Logan's graphical analysis. Brain PET imaging revealed that radioactivities in the hippocampus and the striatum were significantly lower in 5xFAD mice compared to control animals...
May 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29413525/synaptotoxic-signaling-by-amyloid-beta-oligomers-in-alzheimer-s-disease-through-prion-protein-and-mglur5
#16
A Harrison Brody, Stephen M Strittmatter
Alzheimer's disease (AD) represents an impending global health crisis, yet the complexity of AD pathophysiology has so far precluded the development of any interventions to successfully slow or halt AD progression. It is clear that accumulation of Amyloid-beta (Aβ) peptide triggers progressive synapse loss to cause AD symptoms. Once initiated by Aβ, disease progression is complicated and accelerated by inflammation and by tau pathology. The recognition that Aβ peptide assumes multiple distinct states and that soluble oligomeric species (Aβo) are critical for synaptic damage is central to molecular understanding of AD...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29397283/the-metaplastic-effects-of-nmda-receptors-blockade-on-reactivation-of-instrumental-memories-in-rats
#17
Alessandro Piva, Elisabetta Gerace, Marzia Di Chio, Lisa Osanni, Laura Padovani, Lucia Caffino, Fabio Fumagalli, Domenico E Pellegrini-Giampietro, Cristiano Chiamulera
Metaplasticity, defined as the plasticity of synaptic plasticity, could affect learning and memory at different neural levels. It was hypothesized that metaplasticity changes on glutamate receptors may affect memory destabilization, promoting or preventing reconsolidation. We investigated the metaplastic effect of NMDA channel blocker MK-801 on sucrose instrumental memory reconsolidation in a behavioural rat model associated to the assessment of molecular markers of metaplasticity, memory retrieval, destabilization and reconsolidation...
February 12, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29387966/glutamatergic-mechanisms-in-l-dopa-induced-dyskinesia-and-therapeutic-implications
#18
Manuela Mellone, Fabrizio Gardoni
Overactivation of the glutamatergic synapse leading to maladaptive synaptic plasticity in the basal ganglia is a well-demonstrated process involved in the onset of L-DOPA-induced dyskinesia (LID). Changes in glutamate release are paralleled by compensatory modifications of the expression and/or synaptic localization of both ionotropic and metabotropic glutamate receptors (mGluRs). Accordingly, compounds targeting N-methyl-D-aspartate glutamate receptors (NMDARs) and specific subtypes of metabotropic glutamate receptors (mGluR4 and mGluR5) have been tested both in preclinical and clinical studies...
January 31, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29366625/involvement-of-mglur-i-in-ephb-ephrinb-reverse-signaling-activation-induced-retinal-ganglion-cell-apoptosis-in-a-rat-chronic-hypertension-model
#19
Yuan Zhao, Qian Li, Xue-Yan Li, Peng Cui, Feng Gao, Ke Zhu, Ling-Zhu Li, Xing-Huai Sun, Zhongfeng Wang
EphB/ephrinB reverse signaling is involved in retinal ganglion cell (RGC) apoptosis in experimental glaucoma. Here, we further investigated the mechanisms underlying EphB/ephrinB reverse signaling activation induced RGC apoptosis in a rat chronic ocular hypertension (COH) model, using patch-clamp techniques in retinal slices. In COH retinas, RGCs showed higher spontaneous firing frequency and much more depolarized membrane potential as compared to control, which was mimicked by intravitreally injection of EphB2-Fc, an activator of ephrinB2...
March 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29360756/selective-blockade-of-the-metabotropic-glutamate-receptor-mglur5-protects-mouse-livers-in-in-vitro-and-ex-vivo-models-of-ischemia-reperfusion-injury
#20
Andrea Ferrigno, Clarissa Berardo, Laura Giuseppina Di Pasqua, Veronica Siciliano, Plinio Richelmi, Ferdinando Nicoletti, Mariapia Vairetti
2-Methyl-6-(phenylethynyl)pyridine (MPEP), a negative allosteric modulator of the metabotropic glutamate receptor (mGluR) 5, protects hepatocytes from ischemic injury. In astrocytes and microglia, MPEP depletes ATP. These findings seem to be self-contradictory, since ATP depletion is a fundamental stressor in ischemia. This study attempted to reconstruct the mechanism of MPEP-mediated ATP depletion and the consequences of ATP depletion on protection against ischemic injury. We compared the effects of MPEP and other mGluR5 negative modulators on ATP concentration when measured in rat hepatocytes and acellular solutions...
January 23, 2018: International Journal of Molecular Sciences
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