Differential effects of chronic hyperammonemia on modulation of the glutamate–nitric oxide–cGMP pathway by metabotropic glutamate receptor 5 and low and high affinity AMPA receptors in cerebellum in vivo

2012 ◽  
Vol 61 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Andrea Cabrera-Pastor ◽  
Marta Llansola ◽  
Vitaliy Reznikov ◽  
Jordi Boix ◽  
Vicente Felipo
Keyword(s):  
Nitric Oxide ◽  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate Receptor 5 ◽  
Differential Effects ◽  
Metabotropic Glutamate ◽  
High Affinity ◽  
Cgmp Pathway

Evidence that the metabotropic glutamate receptor 5 antagonist MPEP may act as an inhibitor of the norepinephrine transporter in vitro and in vivo

Synapse ◽  
2003 ◽  
Vol 50 (4) ◽  
pp. 269-276 ◽  
Author(s):  
Christian A. Heidbreder ◽  
Massimiliano Bianchi ◽  
Laurent P. Lacroix ◽  
Stefania Faedo ◽  
Elisabetta Perdona ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Norepinephrine Transporter ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate

scholarly journals Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function

2020 ◽  
Author(s):  
Gordon B. Feld ◽  
Til Ole Bergmann ◽  
Marjan Alizadeh-Asfestani ◽  
Viola Stuke ◽  
Jan-Philipp Wriede ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Declarative Memory ◽  
Memory Function ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate ◽  
Healthy Humans ◽  
Procedural Task ◽  
Nonrem Sleep

AbstractSleep consolidates declarative memory by the repeated replay of neuronal traces encoded during prior wakefulness. This replay during sleep is linked to the cardinal oscillations of NonREM sleep. Although this replay is ideally suited to support plasticity, there is so far little evidence of classical glutamatergic plasticity playing a role in this process. To the contrary, we have previously reported that blocking NMDA or AMPA receptors does not affect sleep-dependent consolidation of declarative memory. Here, in two placebo-controlled within-subject cross-over experiments with 20 healthy humans each, we used fenobam to block metabotropic glutamate receptor 5 (mGluR5) during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) during the evening before being administered the treatment and then sleeping for 8 hours – recall was tested in the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II, participants learned new word-pairs in the morning after sleep. Surprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memory-relevant EEG oscillations. In NonREM sleep, fenobam suppressed 12-15 Hz spindles but augmented 2-4 Hz delta waves, whereas in REM sleep it suppressed 4-8 Hz theta and 16-22 Hz beta waves. Notably, under Fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation. Our findings indicates that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations.

scholarly journals Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence

2017 ◽  
Vol 114 (31) ◽  
pp. 8390-8395 ◽  
Author(s):  
Sophie E. Holmes ◽  
Matthew J. Girgenti ◽  
Margaret T. Davis ◽  
Robert H. Pietrzak ◽  
Nicole DellaGioia ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Molecular Mechanisms ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate ◽  
Positron Emission ◽  
Positive Correlations ◽  
Human Postmortem Tissue ◽  
Glutamate System

Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [18F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs. healthy control (HCs) subjects. In an independent sample of human postmortem tissue, we investigated expression of proteins that have a functional relationship with mGluR5 and glucocorticoids in PTSD. We observed significantly higher cortical mGluR5 availability in PTSD in vivo and positive correlations between mGluR5 availability and avoidance symptoms. In the postmortem sample, we observed up-regulation of SHANK1, a protein that anchors mGluR5 to the cell surface, as well as decreased expression of FKBP5, implicating aberrant glucocorticoid functioning in PTSD. Results of this study provide insight into molecular mechanisms underlying PTSD and suggest that mGluR5 may be a promising target for mechanism-based treatments aimed at mitigating this disorder.

scholarly journals Positive allosteric modulation of metabotropic glutamate receptor 5 modulates Akt and GSK3β signaling in vivo

2019 ◽  
Author(s):  
Kari A. Johnson ◽  
P. Jeffrey Conn
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Dorsal Striatum ◽  
Experimental Models ◽  
Male Rats ◽  
Metabotropic Glutamate Receptor 5 ◽  
Akt Phosphorylation ◽  
Metabotropic Glutamate ◽  
Antipsychotic Activity

AbstractBackgroundPositive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) have behavioral effects predictive of antipsychotic activity in experimental models such as amphetamine-induced hyperlocomotion (AHL). However, the signaling mechanisms that contribute to the antipsychotic-like properties of mGlu5 PAMs are not well understood.MethodsBecause the Akt/GSK3β pathway has been implicated in schizophrenia and is modulated by known antipsychotic drugs, we evaluated the effects of systemic administration of two mGlu5 PAMs on Akt and GSK3β signaling using western blot analysis in both naïve and amphetamine-treated adult male rats.ResultsIn the dorsal striatum, the mGlu5-selective PAM VU0092273 (30 mg/kg) significantly increased Akt phosphorylation at residues associated with enhanced kinase activity, Thr308 and Ser473. Inhibitory phosphorylation of GSK3β at Ser9 was also increased. Similar effects were observed with a second mGlu5 PAM, VU0360172 (56.6 mg/kg). VU0092273 increased Akt phosphorylation levels in amphetamine-treated rats. Effects on Akt/GSK3β signaling were not limited to the striatum, as VU0092273 also increased Akt/GSK3β phosphorylation in the medial prefrontal cortex.ConclusionsThese findings suggest that mGlu5 PAMs that have antipsychotic-like efficacy in rats affect signaling pathways that are modulated by known antipsychotics, and raise the possibility that inhibition of GSK3β might contribute to the antipsychotic-like effects of mGlu5 PAMs.

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