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<t>mGluR5</t> expression is modulated with glutamate release in the synapse. A: mGluR5 expressed on the cell surface with low levels of endogenous glutamate. The PET tracer binds to the surface receptors. B: Although glutamate and the PET tracer do not bind to the same location on the mGluR5, when glutamate is released into the synapse, mGluR5 is downregulated/internalized with less receptors being available on the cell surface. Because the PET tracer can bind only to the surface receptors, the binding decreases.
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<t>mGluR5</t> expression is modulated with glutamate release in the synapse. A: mGluR5 expressed on the cell surface with low levels of endogenous glutamate. The PET tracer binds to the surface receptors. B: Although glutamate and the PET tracer do not bind to the same location on the mGluR5, when glutamate is released into the synapse, mGluR5 is downregulated/internalized with less receptors being available on the cell surface. Because the PET tracer can bind only to the surface receptors, the binding decreases.
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<t>mGluR5</t> expression is modulated with glutamate release in the synapse. A: mGluR5 expressed on the cell surface with low levels of endogenous glutamate. The PET tracer binds to the surface receptors. B: Although glutamate and the PET tracer do not bind to the same location on the mGluR5, when glutamate is released into the synapse, mGluR5 is downregulated/internalized with less receptors being available on the cell surface. Because the PET tracer can bind only to the surface receptors, the binding decreases.
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<t>mGluR5</t> expression is modulated with glutamate release in the synapse. A: mGluR5 expressed on the cell surface with low levels of endogenous glutamate. The PET tracer binds to the surface receptors. B: Although glutamate and the PET tracer do not bind to the same location on the mGluR5, when glutamate is released into the synapse, mGluR5 is downregulated/internalized with less receptors being available on the cell surface. Because the PET tracer can bind only to the surface receptors, the binding decreases.
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Image Search Results


mGluR5 expression is modulated with glutamate release in the synapse. A: mGluR5 expressed on the cell surface with low levels of endogenous glutamate. The PET tracer binds to the surface receptors. B: Although glutamate and the PET tracer do not bind to the same location on the mGluR5, when glutamate is released into the synapse, mGluR5 is downregulated/internalized with less receptors being available on the cell surface. Because the PET tracer can bind only to the surface receptors, the binding decreases.

Journal: Biological psychiatry

Article Title: mGluR5 and Stress Disorders: Knowledge Gained from Receptor Imaging Studies

doi: 10.1016/j.biopsych.2017.08.025

Figure Lengend Snippet: mGluR5 expression is modulated with glutamate release in the synapse. A: mGluR5 expressed on the cell surface with low levels of endogenous glutamate. The PET tracer binds to the surface receptors. B: Although glutamate and the PET tracer do not bind to the same location on the mGluR5, when glutamate is released into the synapse, mGluR5 is downregulated/internalized with less receptors being available on the cell surface. Because the PET tracer can bind only to the surface receptors, the binding decreases.

Article Snippet: Our work shows that mGluR5 availability is related to glutamate levels in depression, as well as following a drug challenge, suggesting normalization of glutamate neurotransmission via modulation at mGluR5 may be a needed component in treating some psychiatric disorders or symptoms. table ft1 table-wrap mode="anchored" t5 caption a7 Major Depressive Disorder Animal Studies Agent Mechanism of Action on mGluR5 Finding GRN-529 (Wyeth Pharmaceuticals) NAM Dose-dependent efficacy demonstrated in mice models (decreased immobility time in tail suspension and FST)( 85 ) MPEP 2-Methyl-6-(phenylethynyl)pyridine Antagonist Decreased mobility in the FST Reduced immobility in wild-type mice( 83 ) MTEP 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) Antagonist Decreased mobility in the in the FST( 83 ) Human Studies Basimglurant (code: RG 7090, RO4917523, Roche and Chugai Pharmaceutical) NAM No difference in MADRS scores between adjunctive Basimglurant MR and placebo.

Techniques: Expressing, Binding Assay

mGluR5 radioligands bind to receptors at the cell surface only. Images adapted from (147). A. In a healthy individual, there is a balance in protein expression and mGluR5 number at the cell surface on the post-synaptic dendrite. B. In PTSD, there is a hypothesized increase in scaffolding protein Shank1, which anchors extra mGluR5s to the cell surface. Thus, although the number of mGluR5s may be the same in the healthy and PTSD brain, due the upregulation in Shank1, and thus increase in mGluR5 on the cell surface, quantification of mGluR5 shows higher receptor density.

Journal: Biological psychiatry

Article Title: mGluR5 and Stress Disorders: Knowledge Gained from Receptor Imaging Studies

doi: 10.1016/j.biopsych.2017.08.025

Figure Lengend Snippet: mGluR5 radioligands bind to receptors at the cell surface only. Images adapted from (147). A. In a healthy individual, there is a balance in protein expression and mGluR5 number at the cell surface on the post-synaptic dendrite. B. In PTSD, there is a hypothesized increase in scaffolding protein Shank1, which anchors extra mGluR5s to the cell surface. Thus, although the number of mGluR5s may be the same in the healthy and PTSD brain, due the upregulation in Shank1, and thus increase in mGluR5 on the cell surface, quantification of mGluR5 shows higher receptor density.

Article Snippet: Our work shows that mGluR5 availability is related to glutamate levels in depression, as well as following a drug challenge, suggesting normalization of glutamate neurotransmission via modulation at mGluR5 may be a needed component in treating some psychiatric disorders or symptoms. table ft1 table-wrap mode="anchored" t5 caption a7 Major Depressive Disorder Animal Studies Agent Mechanism of Action on mGluR5 Finding GRN-529 (Wyeth Pharmaceuticals) NAM Dose-dependent efficacy demonstrated in mice models (decreased immobility time in tail suspension and FST)( 85 ) MPEP 2-Methyl-6-(phenylethynyl)pyridine Antagonist Decreased mobility in the FST Reduced immobility in wild-type mice( 83 ) MTEP 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) Antagonist Decreased mobility in the in the FST( 83 ) Human Studies Basimglurant (code: RG 7090, RO4917523, Roche and Chugai Pharmaceutical) NAM No difference in MADRS scores between adjunctive Basimglurant MR and placebo.

Techniques: Expressing, Scaffolding

Summary of preclinical and clinical studies utilizing mGluR5 treatments. See text and Supplementary Material for details.

Journal: Biological psychiatry

Article Title: mGluR5 and Stress Disorders: Knowledge Gained from Receptor Imaging Studies

doi: 10.1016/j.biopsych.2017.08.025

Figure Lengend Snippet: Summary of preclinical and clinical studies utilizing mGluR5 treatments. See text and Supplementary Material for details.

Article Snippet: Our work shows that mGluR5 availability is related to glutamate levels in depression, as well as following a drug challenge, suggesting normalization of glutamate neurotransmission via modulation at mGluR5 may be a needed component in treating some psychiatric disorders or symptoms. table ft1 table-wrap mode="anchored" t5 caption a7 Major Depressive Disorder Animal Studies Agent Mechanism of Action on mGluR5 Finding GRN-529 (Wyeth Pharmaceuticals) NAM Dose-dependent efficacy demonstrated in mice models (decreased immobility time in tail suspension and FST)( 85 ) MPEP 2-Methyl-6-(phenylethynyl)pyridine Antagonist Decreased mobility in the FST Reduced immobility in wild-type mice( 83 ) MTEP 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) Antagonist Decreased mobility in the in the FST( 83 ) Human Studies Basimglurant (code: RG 7090, RO4917523, Roche and Chugai Pharmaceutical) NAM No difference in MADRS scores between adjunctive Basimglurant MR and placebo.

Techniques: Suspension