Metabotropic glutamate 2/3 receptors and epigenetic modifications in psychotic disorders: A review

Francesco Matriscianoa, Isabella Panaccione, Danis R. Grayson, Ferdinando Nicoletti, Alessandro Guidotti

Research output: Contribution to journalArticle

13 Citations (Scopus)

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. In this review, we will discuss in more details the specific features of the PRS mice as a suitable epigenetic model for major psychosis. We will then focus on key proteins of chromatin remodeling machinery as potential target for new pharmacological treatment through the activation of metabotropic glutamate receptors.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalCurrent Neuropharmacology
Volume14
Issue number1
Publication statusPublished - Jan 1 2016

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Epigenomics
Psychotic Disorders
Schizophrenia
Pharmacology
Gene-Environment Interaction
Metabotropic Glutamate Receptors
Chromatin Assembly and Disassembly
Brain-Derived Neurotrophic Factor
Frontal Lobe
DNA Methylation
Locomotion
Interpersonal Relations
Bipolar Disorder
Psychiatry
Proteins
Therapeutics
Animal Models
metabotropic glutamate receptor 3
metabotropic glutamate receptor 2
Genes

Keywords

  • DNA methylation
  • Epigenetics
  • MGlu receptors
  • Prenatal stress
  • Psychosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Pharmacology (medical)
  • Pharmacology
  • Neurology
  • Psychiatry and Mental health

Cite this

Metabotropic glutamate 2/3 receptors and epigenetic modifications in psychotic disorders : A review. / Matriscianoa, Francesco; Panaccione, Isabella; Grayson, Danis R.; Nicoletti, Ferdinando; Guidotti, Alessandro.

In: Current Neuropharmacology, Vol. 14, No. 1, 01.01.2016, p. 41-47.

Research output: Contribution to journalArticle

Matriscianoa, F, Panaccione, I, Grayson, DR, Nicoletti, F & Guidotti, A 2016, 'Metabotropic glutamate 2/3 receptors and epigenetic modifications in psychotic disorders: A review', Current Neuropharmacology, vol. 14, no. 1, pp. 41-47.
Matriscianoa, Francesco ; Panaccione, Isabella ; Grayson, Danis R. ; Nicoletti, Ferdinando ; Guidotti, Alessandro. / Metabotropic glutamate 2/3 receptors and epigenetic modifications in psychotic disorders : A review. In: Current Neuropharmacology. 2016 ; Vol. 14, No. 1. pp. 41-47.
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