The Experts below are selected from a list of 61188 Experts worldwide ranked by ideXlab platform
Tracy A Lane - One of the best experts on this subject based on the ideXlab platform.
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metabotropic Glutamate Receptor 3 mglu3 mglur3 grm3 in schizophrenia antibody characterisation and a semi quantitative western blot study
Schizophrenia Research, 2016Co-Authors: Aintzane Garciabea, M A Walker, Thomas M Hyde, Joel E Kleinman, Paul J Harrison, Tracy A LaneAbstract:Background Metabotropic Glutamate Receptor 3 (mGlu3, mGluR3), encoded by GRM3, is a risk gene for schizophrenia and a therapeutic target. It is unclear whether expression of the Receptor is altered in the disorder or related to GRM3 risk genotype. Antibodies used to date to assess mGlu3 in schizophrenia have not been well validated.
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the group ii metabotropic Glutamate Receptor 3 mglur3 mglu3 grm3 expression function and involvement in schizophrenia
Journal of Psychopharmacology, 2008Co-Authors: Paul J Harrison, Louisa Lyon, L J Sartorius, Philip W J Burnet, Tracy A LaneAbstract:Group II metabotropic Glutamate Receptors (mGluRs) comprise mGluR2 (mGlu2; encoded by GRM2) and mGluR3 (mGlu3; encoded by GRM3) and modulate Glutamate neurotransmission and synaptic plasticity. Here we review the expression and function of mGluR3 and its involvement in schizophrenia. mGluR3 is expressed by glia and neurons in many brain regions and has a predominantly presynaptic distribution, consistent with its role as an inhibitory autoReceptor and heteroceptor. mGluR3 splice variants exist in human brain but are of unknown function. Differentiation of mGluR3 from mGluR2 has been problematic because of the lack of selective ligands and antibodies; the available data suggest particular roles for mGluR3 in long-term depression, in glial function and in neuroprotection. Some but not all studies find genetic association of GRM3 polymorphisms with psychosis, with the risk alleles also being associated with schizophrenia-related endophenotypes such as impaired cognition, cortical activation and Glutamate markers. The dimeric form of mGluR3 may be reduced in the brain in schizophrenia. Finally, preclinical findings have made mGluR3 a putative therapeutic target, and now direct evidence for antipsychotic efficacy of a group II mGluR agonist has emerged from a randomised clinical trial in schizophrenia. Together these data implicate mGluR3 in aetiological, pathophysiological and pharmacotherapeutic aspects of the disorder.
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the group ii metabotropic Glutamate Receptor 3 mglur3 mglu3 grm3 expression function and involvement in schizophrenia
Journal of Psychopharmacology, 2008Co-Authors: Paul J Harrison, Louisa Lyon, L J Sartorius, Philip W J Burnet, Tracy A LaneAbstract:Group II metabotropic Glutamate Receptors (mGluRs) comprise mGluR2 (mGlu2; encoded by GRM2) and mGluR3 (mGlu3; encoded by GRM3) and modulate Glutamate neurotransmission and synaptic plasticity. Here we review the expression and function of mGluR3 and its involvement in schizophrenia. mGluR3 is expressed by glia and neurons in many brain regions and has a predominantly presynaptic distribution, consistent with its role as an inhibitory autoReceptor and heteroceptor. mGluR3 splice variants exist in human brain but are of unknown function. Differentiation of mGluR3 from mGluR2 has been problematic because of the lack of selective ligands and antibodies; the available data suggest particular roles for mGluR3 in long-term depression, in glial function and in neuroprotection. Some but not all studies find genetic association of GRM3 polymorphisms with psychosis, with the risk alleles also being associated with schizophrenia-related endophenotypes such as impaired cognition, cortical activation and Glutamate mar...
Daniel R. Weinberger - One of the best experts on this subject based on the ideXlab platform.
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association of missense mutation in folh1 with decreased naag levels and impaired working memory circuitry and cognition
American Journal of Psychiatry, 2020Co-Authors: Caroline F Zink, Daniel R. Weinberger, Qiang Chen, Peter B Barker, Akira Sawa, Min Wang, Henry M Quillian, William S Ulrich, Andrew E Jaffe, Joel E KleinmanAbstract:Objective:Altering the metabotropic Glutamate Receptor 3 (mGluR3) by pharmacology or genetics is associated with differences in learning and memory in animals and humans. GRM3 (the gene coding for ...
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epistasis between catechol o methyltransferase and type ii metabotropic Glutamate Receptor 3 genes on working memory brain function
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Qiang Chen, Steven Sust, John D Meyers, Michael F Egan, Venkata S Mattay, Joshua W Buckholtz, Daniel R. Weinberger, Andreas Meyerlindenberg, Joseph H CallicottAbstract:Dopaminergic and Glutamatergic systems are critical components responsible for prefrontal signal-to-noise tuning in working memory. Recent functional MRI (fMRI) studies of genetic variation in these systems in catechol-O-methyltransferase (COMT) and in metabotropic Glutamate Receptor mgluR3 (GRM3), respectively, suggest that these genes influence prefrontal physiological signal-to-noise in humans. Here, using fMRI, we extend these individual gene findings to examine the combined effects of COMT and GRM3 on dissociable components of the frontoparietal working memory network. We observed an apparent epistatic interaction of these two genes on the engagement of prefrontal cortex during working memory. Specifically, the GRM3 genotype putatively associated with suboptimal Glutamatergic signaling was significantly associated with inefficient prefrontal engagement and altered prefrontal-parietal coupling on the background of COMT Val-homozygous genotype. Conversely, COMT Met-homozygous background mediated against the effect of GRM3 genotype. These findings extend putative brain dopaminergic and Glutamatergic relationships indexed by COMT and GRM3 to a systems-level interaction in human cortical circuits implicated in working memory dysfunction such as in schizophrenia.
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effect of metabotropic Glutamate Receptor 3 genotype on n acetylaspartate measures in the dorsolateral prefrontal cortex
American Journal of Psychiatry, 2006Co-Authors: Stefano Marenco, Michael F Egan, Sonya Steele, Terry E Goldberg, Richard E Straub, Anjail Z Sharrief, Daniel R. WeinbergerAbstract:Objective: This study was carried out to confirm prior evidence of an effect of a single nucleotide polymorphism (SNP) in the metabotropic Glutamate Receptor 3 (GRM3) gene (a putative risk factor for schizophrenia) on measures of N -acetylaspartate in healthy comparison subjects. Method: Fifty-four carefully screened healthy volunteers genotyped at SNP rs6465084 underwent magnetic resonance spectroscopic imaging (MRSI) at 3 T and selected neuropsychological testing. Results: The A/A genotype group exhibited a significant reduction of N -acetylaspartate/creatine levels in the right dorsolateral prefrontal cortex compared to the G carriers. A tendency in the same direction was seen in the left dorsolateral prefrontal cortex and in the white matter adjacent to the prefrontal cortex. Conclusions: These findings provide further evidence that GRM3 affects prefrontal function and that variation in GRM3, monitored by SNP rs6465084, affects GRM3 function.
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alternative splicing of human metabotropic Glutamate Receptor 3
Journal of Neurochemistry, 2006Co-Authors: Leah Sartorius, Daniel R. Weinberger, Guhan Nagappan, Barbara K Lipska, Yoshitatsu Sei, Renee Renpatterson, Paul HarrisonAbstract:The metabotropic Glutamate Receptor 3 (GRM3, mGluR3) is important in regulating synaptic Glutamate. Here, we report the existence of three splice variants of GRM3 in human brain arising from exon skipping events. The transcripts are expressed in prefrontal cortex, hippocampus and cerebellum, and in B lymphoblasts. We found no evidence for alternative splicing of GRM2. The most abundant GRM3 variant lacks exon 4 (GRM3Δ4). In silico translation analysis of GRM3Δ4 predicts a truncated protein with a conserved extracellular ligand binding domain, absence of a seven-transmembrane domain, and a unique 96-amino acid C-terminus. When expressed in rat hippocampal neurons, GRM3Δ4 is translated into a 60 kDa protein. Immunostaining and cell fractionation data indicate that the truncated protein is primarily membrane-associated. An antibody developed against the GRM3Δ4 C-terminus detects a protein of approximately 60 kDa in human brain lysates and in B lymphoblasts, suggesting translation of GRM3Δ4 in vivo. The existence of the GRM3Δ4 isoform is relevant in the light of the reported association of non-coding single nucleotide polymorphisms (SNPs) in GRM3 with schizophrenia, and with the potential of GRM3 as a therapeutic target for several neuropsychiatric disorders.
Paul J Harrison - One of the best experts on this subject based on the ideXlab platform.
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metabotropic Glutamate Receptor 3 mglu3 mglur3 grm3 in schizophrenia antibody characterisation and a semi quantitative western blot study
Schizophrenia Research, 2016Co-Authors: Aintzane Garciabea, M A Walker, Thomas M Hyde, Joel E Kleinman, Paul J Harrison, Tracy A LaneAbstract:Background Metabotropic Glutamate Receptor 3 (mGlu3, mGluR3), encoded by GRM3, is a risk gene for schizophrenia and a therapeutic target. It is unclear whether expression of the Receptor is altered in the disorder or related to GRM3 risk genotype. Antibodies used to date to assess mGlu3 in schizophrenia have not been well validated.
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the group ii metabotropic Glutamate Receptor 3 mglur3 mglu3 grm3 expression function and involvement in schizophrenia
Journal of Psychopharmacology, 2008Co-Authors: Paul J Harrison, Louisa Lyon, L J Sartorius, Philip W J Burnet, Tracy A LaneAbstract:Group II metabotropic Glutamate Receptors (mGluRs) comprise mGluR2 (mGlu2; encoded by GRM2) and mGluR3 (mGlu3; encoded by GRM3) and modulate Glutamate neurotransmission and synaptic plasticity. Here we review the expression and function of mGluR3 and its involvement in schizophrenia. mGluR3 is expressed by glia and neurons in many brain regions and has a predominantly presynaptic distribution, consistent with its role as an inhibitory autoReceptor and heteroceptor. mGluR3 splice variants exist in human brain but are of unknown function. Differentiation of mGluR3 from mGluR2 has been problematic because of the lack of selective ligands and antibodies; the available data suggest particular roles for mGluR3 in long-term depression, in glial function and in neuroprotection. Some but not all studies find genetic association of GRM3 polymorphisms with psychosis, with the risk alleles also being associated with schizophrenia-related endophenotypes such as impaired cognition, cortical activation and Glutamate markers. The dimeric form of mGluR3 may be reduced in the brain in schizophrenia. Finally, preclinical findings have made mGluR3 a putative therapeutic target, and now direct evidence for antipsychotic efficacy of a group II mGluR agonist has emerged from a randomised clinical trial in schizophrenia. Together these data implicate mGluR3 in aetiological, pathophysiological and pharmacotherapeutic aspects of the disorder.
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the group ii metabotropic Glutamate Receptor 3 mglur3 mglu3 grm3 expression function and involvement in schizophrenia
Journal of Psychopharmacology, 2008Co-Authors: Paul J Harrison, Louisa Lyon, L J Sartorius, Philip W J Burnet, Tracy A LaneAbstract:Group II metabotropic Glutamate Receptors (mGluRs) comprise mGluR2 (mGlu2; encoded by GRM2) and mGluR3 (mGlu3; encoded by GRM3) and modulate Glutamate neurotransmission and synaptic plasticity. Here we review the expression and function of mGluR3 and its involvement in schizophrenia. mGluR3 is expressed by glia and neurons in many brain regions and has a predominantly presynaptic distribution, consistent with its role as an inhibitory autoReceptor and heteroceptor. mGluR3 splice variants exist in human brain but are of unknown function. Differentiation of mGluR3 from mGluR2 has been problematic because of the lack of selective ligands and antibodies; the available data suggest particular roles for mGluR3 in long-term depression, in glial function and in neuroprotection. Some but not all studies find genetic association of GRM3 polymorphisms with psychosis, with the risk alleles also being associated with schizophrenia-related endophenotypes such as impaired cognition, cortical activation and Glutamate mar...
Jonathan Picker - One of the best experts on this subject based on the ideXlab platform.
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phenotypic characterization of mice heterozygous for a null mutation of Glutamate carboxypeptidase ii
Synapse, 2009Co-Authors: Jonathan Picker, Guochuan Tsai, Zhichun Jiang, Laura Schaevitz, Jiamin Feng, Alo C. Basu, Joanne BergersweeneyAbstract:Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbed Glutamate signaling resulting in hypofunction of N-methyl-D-aspartate Receptors (NMDAR) has been implicated in the pathophysiology of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes N-acetyl-alpha L-aspartyl-L-Glutamate (NAAG) into Glutamate and N-acetyl-aspartate. NAAG is a neuropeptide that is an NMDAR antagonist as well as an agonist for the metabotropic Glutamate Receptor-3 (mGluR3), which inhibits Glutamate release. The aggregate effect of NAAG is thus to attenuate NMDAR activation. To manipulate the expression of GCP II, LoxP sites were inserted flanking exons 1 and 2, which were excised by crossing with a Cre-expressing mouse. The mice heterozygous for this deletion showed a 50% reduction in the expression level of protein and functional activity of GCP II in brain samples. Heterozygous mutant crosses did not yield any homozygous null animals at birth or as embryos (N > 200 live births and fetuses). These data are consistent with the previous report that GCP II homozygous mutant mice generated by removing exons 9 and 10 of GCP II gene were embryonically lethal and confirm our hypothesis that GCP II plays an essential role early in embryonic development. Heterozygous mice, however, developed normally to adulthood and exhibited increased locomotor activity, reduced social interaction, and a subtle cognitive deficit in working memory. Synapse 63:625–635, 2009. © 2009 Wiley-Liss, Inc.
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Phenotypic characterization of mice heterozygous for a null mutation of Glutamate carboxypeptidase II.
Synapse, 2009Co-Authors: Liqun Han, Guochuan Tsai, Zhichun Jiang, Jonathan Picker, Laura Schaevitz, Jiamin Feng, Hillary C. Chu, Alo C. Basu, Joanne Berger-sweeney, Joseph T CoyleAbstract:Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbed Glutamate signaling resulting in hypofunction of N-methyl-D-aspartate Receptors (NMDAR) has been implicated in the pathophysiology of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes N-acetyl-alpha L-aspartyl-L-Glutamate (NAAG) into Glutamate and N-acetyl-aspartate. NAAG is a neuropeptide that is an NMDAR antagonist as well as an agonist for the metabotropic Glutamate Receptor-3 (mGluR3), which inhibits Glutamate release. The aggregate effect of NAAG is thus to attenuate NMDAR activation. To manipulate the expression of GCP II, LoxP sites were inserted flanking exons 1 and 2, which were excised by crossing with a Cre-expressing mouse. The mice heterozygous for this deletion showed a 50% reduction in the expression level of protein and functional activity of GCP II in brain samples. Heterozygous mutant crosses did not yield any homozygous null animals at birth or as embryos (N > 200 live births and fetuses). These data are consistent with the previous report that GCP II homozygous mutant mice generated by removing exons 9 and 10 of GCP II gene were embryonically lethal and confirm our hypothesis that GCP II plays an essential role early in embryonic development. Heterozygous mice, however, developed normally to adulthood and exhibited increased locomotor activity, reduced social interaction, and a subtle cognitive deficit in working memory.
Michael F Egan - One of the best experts on this subject based on the ideXlab platform.
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epistasis between catechol o methyltransferase and type ii metabotropic Glutamate Receptor 3 genes on working memory brain function
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Qiang Chen, Steven Sust, John D Meyers, Michael F Egan, Venkata S Mattay, Joshua W Buckholtz, Daniel R. Weinberger, Andreas Meyerlindenberg, Joseph H CallicottAbstract:Dopaminergic and Glutamatergic systems are critical components responsible for prefrontal signal-to-noise tuning in working memory. Recent functional MRI (fMRI) studies of genetic variation in these systems in catechol-O-methyltransferase (COMT) and in metabotropic Glutamate Receptor mgluR3 (GRM3), respectively, suggest that these genes influence prefrontal physiological signal-to-noise in humans. Here, using fMRI, we extend these individual gene findings to examine the combined effects of COMT and GRM3 on dissociable components of the frontoparietal working memory network. We observed an apparent epistatic interaction of these two genes on the engagement of prefrontal cortex during working memory. Specifically, the GRM3 genotype putatively associated with suboptimal Glutamatergic signaling was significantly associated with inefficient prefrontal engagement and altered prefrontal-parietal coupling on the background of COMT Val-homozygous genotype. Conversely, COMT Met-homozygous background mediated against the effect of GRM3 genotype. These findings extend putative brain dopaminergic and Glutamatergic relationships indexed by COMT and GRM3 to a systems-level interaction in human cortical circuits implicated in working memory dysfunction such as in schizophrenia.
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effect of metabotropic Glutamate Receptor 3 genotype on n acetylaspartate measures in the dorsolateral prefrontal cortex
American Journal of Psychiatry, 2006Co-Authors: Stefano Marenco, Michael F Egan, Sonya Steele, Terry E Goldberg, Richard E Straub, Anjail Z Sharrief, Daniel R. WeinbergerAbstract:Objective: This study was carried out to confirm prior evidence of an effect of a single nucleotide polymorphism (SNP) in the metabotropic Glutamate Receptor 3 (GRM3) gene (a putative risk factor for schizophrenia) on measures of N -acetylaspartate in healthy comparison subjects. Method: Fifty-four carefully screened healthy volunteers genotyped at SNP rs6465084 underwent magnetic resonance spectroscopic imaging (MRSI) at 3 T and selected neuropsychological testing. Results: The A/A genotype group exhibited a significant reduction of N -acetylaspartate/creatine levels in the right dorsolateral prefrontal cortex compared to the G carriers. A tendency in the same direction was seen in the left dorsolateral prefrontal cortex and in the white matter adjacent to the prefrontal cortex. Conclusions: These findings provide further evidence that GRM3 affects prefrontal function and that variation in GRM3, monitored by SNP rs6465084, affects GRM3 function.