ArticleThe American journal of psychiatry2009
Differential expression of metabotropic glutamate receptors 2 and 3 in schizophrenia: a mechanism for antipsychotic drug action?
Article in The American journal of psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis.The American journal of psychiatry · 2010Pooled it
- Effect of mGluR2 positive allosteric modulation on frontostriatal working memory activation in schizophrenia.Molecular psychiatry · 2022Trial
- Cryo-EM Structures of Brain-Derived G Protein-Coupled Receptors: The First Direct Visualization from Mammalian Brain Tissue.bioRxiv : the preprint server for biology · 2026Article
- Post-methamphetamine working memory decline predicts relapse vulnerability in rats and is rescued by mGlu3 receptor activation.Psychopharmacology · 2026Article
- A genome-wide association study reveals a polygenic architecture of speech-in-noise deficits in individuals with self-reported normal hearing.Scientific reports · 2024Article
- The role of thalamic group II mGlu receptors in health and disease.Neuronal signaling · 2022Review
- Inhibition of glutamate-carboxypeptidase-II in dorsolateral prefrontal cortex: potential therapeutic target for neuroinflammatory cognitive disorders.Molecular psychiatry · 2022Article
- Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia.Biological psychiatry · 2022Review
- Review
- Glutamate Metabotropic Receptor Type 3 (mGlu3) Localization in the Rat Prelimbic Medial Prefrontal Cortex.Frontiers in neuroanatomy · 2022Article
- The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex.Molecular psychiatry · 2021Review
- Gene-expression correlates of the oscillatory signatures supporting human episodic memory encoding.Nature neuroscience · 2021Article
- Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance.Frontiers in aging neuroscience · 2021Article
- Regulation of Glutamatergic Activity via Bidirectional Activation of Two Select Receptors as a Novel Approach in Antipsychotic Drug Discovery.International journal of molecular sciences · 2020Review
- Unique Molecular Regulation of Higher-Order Prefrontal Cortical Circuits: Insights into the Neurobiology of Schizophrenia.ACS chemical neuroscience · 2018Review
- mGluR2 versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Neurobiological Determinants of Tobacco Smoking in Schizophrenia.Frontiers in psychiatry · 2018Review
- mGluR2/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both presynaptic and postsynaptic actions.Molecular psychiatry · 2017Article
- Metabotropic glutamate receptor 3 (mGlu3; mGluR3; GRM3) in schizophrenia: Antibody characterisation and a semi-quantitative western blot study.Schizophrenia research · 2016Article
- COMT val158met polymorphism and molecular alterations in the human dorsolateral prefrontal cortex: Differences in controls and in schizophrenia.Schizophrenia research · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectivePreclinical and clinical data implicate the group II metabotropic glutamate receptors mGluR2 and mGluR3 in the pathophysiology of schizophrenia. Moreover, a recent phase II clinical trial demonstrated the antipsychotic efficacy of a mGluR2/mGluR3 agonist. The purpose of the present study was to distinguish the expression of mGluR2 and mGluR3 receptor proteins in schizophrenia and to quantify glutamate carboxypeptidase II (GCP II) in order to explore a role for the metabotropic receptors in schizophrenia therapeutics. GCP II is an enzyme that metabolizes N-acetyl-aspartyl-glutamate (NAAG), which is the only known specific endogenous agonist of mGluR3 in the mammalian brain.
methodThe normal expression levels of mGluR2, mGluR3, and GCP II were determined for 10 regions of the postmortem human brain using specific antibodies. Differences in expression levels of each protein were examined in the dorsolateral prefrontal cortex, temporal cortex, and motor cortex in 15 postmortem schizophrenia subjects and 15 postmortem matched normal comparison subjects. Chronic antipsychotic treatment in rodents was conducted to examine the potential effect of antipsychotic drugs on expression of the three proteins.
resultsFindings revealed a significant increase in GCP II protein and a reduction in mGluR3 protein in the dorsolateral prefrontal cortex in schizophrenia subjects, with mGluR2 protein levels unchanged. Chronic antipsychotic treatment in rodents did not influence GCP II or mGluR3 levels.
conclusionsIncreased GCP II expression and low mGluR3 expression in the dorsolateral prefrontal cortex suggest that NAAG-mediated signaling is impaired in this brain region in schizophrenia. Further, these data implicate the mGluR3 receptor in the antipsychotic action of mGluR2/mGluR3 agonists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.