Metabotropic Glutamate 2/3 Receptors and Epigenetic Modifications in Psychotic Disorders: A Review

Current Neuropharmacology
F MatriscianoA Guidotti

Abstract

Schizophrenia and Bipolar Disorder are chronic psychiatric disorders, both considered as "major psychosis"; they are thought to share some pathogenetic factors involving a dysfunctional gene x environment interaction. Alterations in the glutamatergic transmission have been suggested to be involved in the pathogenesis of psychosis. Our group developed an epigenetic model of schizophrenia originated by Prenatal Restraint Stress (PRS) paradigm in mice. PRS mice developed some behavioral alterations observed in schizophrenic patients and classic animal models of schizophrenia, i.e. deficits in social interaction, locomotor activity and prepulse inhibition. They also showed specific changes in promoter DNA methylation activity of genes related to schizophrenia such as reelin, BDNF and GAD67, and altered expression and function of mGlu2/3 receptors in the frontal cortex. Interestingly, behavioral and molecular alterations were reversed by treatment with mGlu2/3 agonists. Based on these findings, we speculate that pharmacological modulation of these receptors could have a great impact on early phase treatment of psychosis together with the possibility to modulate specific epigenetic key protein involved in the development of psychosis...Continue Reading

Citations

Dec 20, 2018·Frontiers in Molecular Neuroscience·Francesco MatriscianoAlessandro Guidotti
Mar 3, 2018·The Journal of Pain : Official Journal of the American Pain Society·Yaping JiRichard J Traub
Aug 28, 2021·Biological Psychiatry·Mariacristina Mazzitelli, Volker Neugebauer

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Methods Mentioned

BETA
acetylation
histone acetylation

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