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.