Upregulation of cornichon transcripts in the dorsolateral prefrontal cortex in schizophrenia

Abstract

Schizophrenia has been proposed to be associated with abnormal glutamatergic neurotransmission. The AMPA subtype of glutamate receptors (AMPARs) mediates fast excitatory synaptic transmission in the brain, and their trafficking and function is regulated in part by AMPAR auxiliary proteins including the cornichons (CNIH) and transmembrane AMPAR-regulatory proteins. Abnormal regulation of AMPARs through altered expression of these auxiliary proteins could induce changes in glutamatergic neurotransmission and thus the pathophysiology of schizophrenia. In this study, transcript expression of cornichon homologs 1-4 was measured in the dorsolateral prefrontal cortex from schizophrenia (N=25) and comparison (N=25) patient groups by comparative quantitative real-time PCR. Significant upregulation of CNIH-1, CNIH-2, and CNIH-3 mRNA expression was found in schizophrenia, with no change in CNIH-4 expression. To determine the effect of antipsychotic treatment on the expression of these genes, cornichon mRNA expression was assayed in the frontal cortex of rats treated chronically with haloperidol decanoate and no changes in any of the cornichon transcripts were found. Abnormal expression of the CNIH family of genes is consistent with cornichon-mediated AMPAR trafficking abnormalities in schizophrenia, and suggests a new mechanism contributing toward the pathophysiology of this illness.