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Metabotropic glutamate receptor

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https://www.readbyqxmd.com/read/28440729/2-arachidonoylglycerol-endocannabinoid-signaling-coupled-to-metabotropic-glutamate-receptor-type-5-modulates-anxiety-like-behavior-in-the-rat-ventromedial-prefrontal-cortex
#1
Ana F Almeida-Santos, Fabricio A Moreira, Francisco S Guimaraes, Daniele C Aguiar
2-Arachidonoylglycerol and anandamide are the main endocannabinoids, which act through cannabinoid type-1 and type-2 receptors. Among its many functions, anandamide modulates anxiety-like behaviors in the ventromedial prefrontal cortex. The role of 2-arachidonoylglycerol in this region, however, has remained unclear. Here, we verified whether intra- ventromedial prefrontal cortex injection of 2-arachidonoylglycerol or URB602, a monoacylglycerol lipase inhibitor (responsible for 2-arachidonoylglycerol hydrolysis), induce anxiolytic-like effects in Wistar rats...
April 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28436626/-the-role-of-central-cholinergic-system-in-epilepsy
#2
Ying Wang, Yi Wang, Zhong Chen
Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy...
January 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28435670/type-1-metabotropic-glutamate-receptor-signaling-in-cerebellar-purkinje-cells-in-health-and-disease
#3
REVIEW
Masanobu Kano, Takaki Watanabe
The cerebellum is a brain structure involved in coordination, control, and learning of movements, as well as certain aspects of cognitive function. Purkinje cells are the sole output neurons from the cerebellar cortex and therefore play crucial roles in the overall function of the cerebellum. The type-1 metabotropic glutamate receptor (mGluR1) is a key "hub" molecule that is critically involved in the regulation of synaptic wiring, excitability, synaptic response, and synaptic plasticity of Purkinje cells. In this review, we aim to highlight how mGluR1 controls these events in Purkinje cells...
2017: F1000Research
https://www.readbyqxmd.com/read/28433499/changes-in-the-expression-of-metabotropic-glutamate-receptor-5-mglur5-in-a-ketamine-based-animal-model-of-schizophrenia
#4
Dariusz Zurawek, Anna Salerno-Kochan, Marta Dziedzicka-Wasylewska, Agnieszka Nikiforuk, Tomasz Kos, Piotr Popik
It has been shown that the metabotropic glutamate receptor subtype 5 (mGluR5) is functionally associated with the NMDA subtype of the glutamate receptor family (NMDA receptors). These two receptors colocalize in brain regions associated with schizophrenia. Although the role of the NMDA receptor in cognitive and negative symptoms of schizophrenia is well studied, information about the role of mGluR5 receptors in schizophrenia is sparse. In our work, we show that subchronic administration of ketamine, a well-studied, non-competitive antagonist of NMDA receptors, caused cognitive deficits in rats as shown by testing novel object recognition (NOR)...
April 19, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28432493/effect-of-pharmacological-modulation-of-activity-of-metabotropic-glutamate-receptors-on-their-gene-expression-after-excitotoxic-damage-in-hippocampal-neurons
#5
E V Pershina, M V Kapralova, V I Arkhipov
Microinjection of kainic acid into rat hippocampus causes excitotoxic neuronal damage predominantly in the CA3 and CA1 fields. These lesions can be significantly reduced by simultaneous administration of MPEP, a negative allosteric modulator of type 5 metabotropic glutamate receptors, and LY354740, an agonist of type 2 metabotropic glutamate receptors. The decrease in neuronal death in the hippocampus during pharmacological modulation was paralleled by adaptive changes in gene expression. In the hippocampus, gene expression of type 5 postsynaptic metabotropic glutamate receptor was close to the control level, and in the frontal cortex expression of the gene of α1-subunit of the GABAA receptor returned to normal...
April 22, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28431287/age-and-gender-effects-of-11-c-itmm-binding-to-metabotropic-glutamate-receptor-type-1-in-healthy-human-participants
#6
Muneyuki Sakata, Jun Toyohara, Kenji Ishibashi, Kei Wagatsuma, Kenji Ishii, Ming-Rong Zhang, Kiichi Ishiwata
We examined possible age- and gender-related changes in binding of the selective antagonist N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM) to metabotropic glutamate receptor type 1 in healthy human brains. Dynamic (11)C-ITMM positron emission tomography scans (90 min) with serial arterial blood sampling were performed in 15 young and 24 older healthy adult volunteers. The total distribution volume (VT) of several brain regions was estimated with 2-tissue compartment model analysis...
March 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28422818/inhibition-of-metabotropic-glutamate-receptor-subtype-1-alters-the-excitability-of-the-commissural-pyramidal-neuron-in-the-rat-anterior-cingulate-cortex-after-chronic-constriction-injury-to-the-sciatic-nerve
#7
Shi-Hao Gao, Lin-Lin Shen, Hui-Zhong Wen, Yan-Dong Zhao, Huai-Zhen Ruan
BACKGROUND: Inhibition of the metabotropic glutamate receptor subtype 1 in the anterior cingulate cortex has an analgesic effect during sustained nociceptive hypersensitivity. However, the specific changes in different subtypes of anterior cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of metabotropic glutamate receptor subtype 1 inhibition on different neuronal subtypes, have not been well studied. METHODS: Retrograde labeling combined with immunofluorescence, whole cell clamp recording, and behavioral tests combined with RNA interference were performed in a rat model of chronic constriction injury to the sciatic nerve...
April 19, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28419871/short-term-inhibition-of-gabaergic-ipscs-induced-by-association-of-pre-and-postsynaptic-activation-in-the-neonatal-hippocampus
#8
Megumi Taketo, Hiroko Matsuda
Activity-dependent plasticity including short and long-term depression accompanied by a reduction in transmitter release probability has been demonstrated in both inhibitory and excitatory synapses. In the neonatal hippocampus, repetitive postsynaptic depolarization is followed by presynaptic alterations of the efficacy of GABAAergic transmission. Both facilitation and inhibition have been observed, but the mechanisms underlying this plasticity have not yet been elucidated. In the present experiment, repetitive postsynaptic depolarization by itself did not cause marked alterations of spontaneous inhibitory postsynaptic currents (sIPSCs)...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28417952/investigating-the-molecular-mechanism-of-positive-and-negative-allosteric-modulators-in-the-calcium-sensing-receptor-dimer
#9
Stine Engesgaard Jacobsen, Ulrik Gether, Hans Bräuner-Osborne
Allosteric modulators that are targeting the calcium-sensing receptor (CaSR) hold great therapeutic potential, and elucidating the molecular basis for modulation would thus benefit the development of novel therapeutics. In the present study, we aimed at investigating the mechanism of allosteric modulation in CaSR by testing dimers carrying mutations in the allosteric site of one or both of the subunits. To ensure measurements on a well-defined dimer composition, we applied a trans-activation system in which only the specific heterodimer of two loss-of-function mutants responded to agonist...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28413831/differential-ability-of-the-dorsal-and-ventral-rat-hippocampus-to-exhibit-group-i-metabotropic-glutamate-receptor-dependent-synaptic-and-intrinsic-plasticity
#10
Patrick Tidball, Hannah V Burn, Kai Lun Teh, Arturas Volianskis, Graham L Collingridge, Stephen M Fitzjohn
BACKGROUND: The hippocampus is critically involved in learning and memory processes. Although once considered a relatively homogenous structure, it is now clear that the hippocampus can be divided along its longitudinal axis into functionally distinct domains, responsible for the encoding of different types of memory or behaviour. Although differences in extrinsic connectivity are likely to contribute to this functional differentiation, emerging evidence now suggests that cellular and molecular differences at the level of local hippocampal circuits may also play a role...
January 2017: Brain Neurosci Adv
https://www.readbyqxmd.com/read/28413623/glutamate-plasticity-woven-through-the-progression-to-alcohol-use-disorder-a-multi-circuit-perspective
#11
REVIEW
Lara Hwa, Joyce Besheer, Thomas Kash
Glutamate signaling in the brain is one of the most studied targets in the alcohol research field. Here, we report the current understanding of how the excitatory neurotransmitter glutamate, its receptors, and its transporters are involved in low, episodic, and heavy alcohol use. Specific animal behavior protocols can be used to assess these different drinking levels, including two-bottle choice, operant self-administration, drinking in the dark, the alcohol deprivation effect, intermittent access to alcohol, and chronic intermittent ethanol vapor inhalation...
2017: F1000Research
https://www.readbyqxmd.com/read/28413097/mglu2-3-receptor-antagonists-as-novel-antidepressants
#12
REVIEW
Shigeyuki Chaki
Based on the discovery of the robust antidepressant effects of ketamine in patients with depression, including those with treatment-resistant depression, agents acting on the glutamatergic system have drawn much attention as potential novel antidepressants. Among the agents acting on the glutamatergic system, preclinical data have indicated that the group II metabotropic glutamate (mGlu) receptors, mGlu2 and mGlu3, are attractive targets for the development of novel antidepressants. The antidepressant effects of mGlu2/3 receptor antagonists have been demonstrated in rodent models, and the synaptic and neural mechanisms underlying the antidepressant effects of these compounds have been investigated...
April 13, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28405888/effects-of-common-grm5-genetic-variants-on-cognition-hippocampal-volume-and-mglur5-protein-levels-in-schizophrenia
#13
Natalie Matosin, Kelly Anne Newell, Yann Quidé, Jessica Lee Andrews, Nina Teroganova, Melissa Jayne Green, Francesca Fernandez
GRM5 (coding for metabotropic glutamate receptor 5, mGluR5) is a promising target for the treatment of cognitive deficits in schizophrenia, but there has been little investigation of its association with cognitive and brain phenotypes within this disorder. We examined the effects of common genetic variation in GRM5 with cognitive function, hippocampal volume, and hippocampal mGluR5 protein levels in schizophrenia patients relative to healthy controls. Two independent GRM5 variants rs60954128 [C>T] and rs3824927 [G>T] were genotyped in a schizophrenia case/control cohort (n=249/261)...
April 13, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28404748/components-of-rna-granules-affect-their-localization-and-dynamics-in-neuronal-dendrites
#14
Kazuhiko Mitsumori, Yosuke Takei, Nobutaka Hirokawa
In neurons, RNA transport is important for local protein synthesis. Messenger RNAs (mRNAs) are transported along dendrites as large RNA granules. The localization and dynamics of Puralpha and Stau1, major components of RNA transport granules, were investigated in cultured hippocampal neurons. Puralpha-positive granules were localized in both the shafts and spines of dendrites. In contrast, Stau1-positive granules tended to be localized mainly in dendritic shafts. More than 90% of Puralpha-positive granules were positive for Stau1 in immature dendrites, while only half were positive in mature dendrites...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28400257/phase-amplitude-coupled-persistent-theta-and-gamma-oscillations-in-rat-primary-motor-cortex-in%C3%A2-vitro
#15
Nicholas W Johnson, Mazhar Özkan, Adrian P Burgess, Emma J Prokic, Keith A Wafford, Michael J O'Neill, Stuart D Greenhill, Ian M Stanford, Gavin L Woodhall
In vivo, theta (4-7 Hz) and gamma (30-80 Hz) neuronal network oscillations are known to coexist and display phase-amplitude coupling (PAC). However, in vitro, these oscillations have for many years been studied in isolation. Using an improved brain slice preparation technique we have, using co-application of carbachol (10 μM) and kainic acid (150 nM), elicited simultaneous theta (6.6 ± 0.1 Hz) and gamma (36.6 ± 0.4 Hz) oscillations in rodent primary motor cortex (M1). Each oscillation showed greatest power in layer V...
April 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28397841/ketamine-induced-reduction-in-mglur5-availability-is-associated-with-an-antidepressant-response-an-11-c-abp688-and-pet-imaging-study-in-depression
#16
I Esterlis, N DellaGioia, R H Pietrzak, D Matuskey, N Nabulsi, C G Abdallah, J Yang, C Pittenger, G Sanacora, J H Krystal, R V Parsey, R E Carson, C DeLorenzo
The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers participated in two [(11)C]ABP688 positron emission tomography (PET) scans on the same day-before and during intravenous ketamine administration-and a third scan 1 day later...
April 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28396447/dual-optical-control-and-mechanistic-insights-into-photoswitchable-group-ii-and-iii-metabotropic-glutamate-receptors
#17
Joshua Levitz, Johannes Broichhagen, Philipp Leippe, David Konrad, Dirk Trauner, Ehud Y Isacoff
G protein-coupled receptor (GPCR) signaling occurs in complex spatiotemporal patterns that are difficult to probe using standard pharmacological and genetic approaches. A powerful approach for dissecting GPCRs is to use light-controlled pharmacological agents that are tethered covalently and specifically to genetically engineered receptors. However, deficits in our understanding of the mechanism of such photoswitches have limited application of this approach and its extension to other GPCRs. In this study, we have harnessed the power of bioorthogonal tethering to SNAP and CLIP protein tags to create a family of light-gated metabotropic glutamate receptors (mGluRs)...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28395733/optical-control-of-pain-in-vivo-with-a-photoactive-mglu5-receptor-negative-allosteric-modulator
#18
Joan Font, Marc López-Cano, Serena Notartomaso, Pamela Scarselli, Paola Di Pietro, Roger Bresolí-Obach, Giuseppe Battaglia, Fanny Malhaire, Xavier Rovira, Juanlo Catena, Jesús Giraldo, Jean-Philippe Pin, Víctor Fernández-Dueñas, Cyril Goudet, Santi Nonell, Ferdinando Nicoletti, Amadeu Llebaria, Francisco Ciruela
Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu5 receptor activity both in ectopic expressing systems and in striatal primary neurons...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28392767/early-onset-network-hyperexcitability-in-presymptomatic-alzheimer-s-disease-transgenic-mice-is-suppressed-by-passive-immunization-with-anti-human-app-a%C3%AE-antibody-and-by-mglur5-blockade
#19
Syed F Kazim, Shih-Chieh Chuang, Wangfa Zhao, Robert K S Wong, Riccardo Bianchi, Khalid Iqbal
Cortical and hippocampal network hyperexcitability appears to be an early event in Alzheimer's disease (AD) pathogenesis, and may contribute to memory impairment. It remains unclear if network hyperexcitability precedes memory impairment in mouse models of AD and what are the underlying cellular mechanisms. We thus evaluated seizure susceptibility and hippocampal network hyperexcitability at ~3 weeks of age [prior to amyloid beta (Aβ) plaque deposition, neurofibrillary pathology, and cognitive impairment] in a triple transgenic mouse model of familial AD (3xTg-AD mouse) that harbors mutated human Aβ precursor protein (APP), tau and presenilin 1 (PS1) genes...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28392321/pharmacological-modulation-of-metabotropic-glutamate-receptor-subtype-5-and-7-impairs-extinction-of-social-fear-in-a-time-point-dependent-manner
#20
David A Slattery, Inga D Neumann, Peter J Flor, Iulia Zoicas
Pharmacological modulation of metabotropic glutamate receptor subtype 5 (mGluR5) and 7 (mGluR7) was shown to attenuate the acquisition and to facilitate the extinction of cued and contextual, non-social, fear. Using the allosteric mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and the allosteric mGluR7 agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), we aimed to study how pharmacological blockade of mGluR5 and activation of mGluR7 influence acquisition and extinction of social fear in mice...
April 7, 2017: Behavioural Brain Research
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