title: 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.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. jdrummond@uab.edu
authors.forename: Jana B
authors.initials: JB
authors.lastname: Drummond
authors.forename: Micah
authors.initials: M
authors.lastname: Simmons
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.forename: James H
authors.initials: JH
authors.lastname: Meador-Woodruff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D004527:Egg Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000502:physiology; D006220:Haloperidol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; C579776:CNIH-1 protein, rat; C118276:CNIH1 protein, human; C539313:Cnih2 protein, rat; C579775:Cnih4 protein, rat; D004527:Egg Proteins; D005819:Genetic Markers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018698:Glutamic Acid; C033563:haloperidol decanoate; D006220:Haloperidol