title: Transmembrane AMPA receptor regulatory protein (TARP) dysregulation in anterior cingulate cortex in schizophrenia.
abstract: The glutamate hypothesis of schizophrenia proposes that abnormal glutamatergic neurotransmission occurs in this illness, and a major contribution may involve dysregulation of the AMPA subtype of ionotropic glutamate receptor (AMPAR). Transmembrane AMPAR regulatory proteins (TARPs) form direct associations with AMPARs to modulate the trafficking and biophysical functions of these receptors, and their dysregulation may alter the localization and activity of AMPARs, thus having a potential role in the pathophysiology of schizophrenia. We performed comparative quantitative real-time PCR and Western blot analysis to measure transcript (schizophrenia, N=25; comparison subjects, N=25) and protein (schizophrenia, N=36; comparison subjects, N=33) expression of TARPs (γ subunits 1-8) in the anterior cingulate cortex (ACC) in schizophrenia and a comparison group. TARP expression was also measured in frontal cortex of rats chronically treated with haloperidol decanoate (28.5mg/kg every three weeks for nine months) to determine the effect of antipsychotic treatment on the expression of these molecules. We found decreased transcript expression of TARP γ-8 in schizophrenia. At the protein level, γ-3 and γ-5 were increased, while γ-4, γ-7 and γ-8 were decreased in schizophrenia. No changes in any of the molecules were noted in the frontal cortex of haloperidol-treated rats. TARPs are abnormally expressed at transcript and protein levels in ACC in schizophrenia, and these changes are likely due to the illness and not to the antipsychotic treatment. Alterations in the expression of TARPs may contribute to the pathophysiology of schizophrenia, and represent a potential mechanism of glutamatergic dysregulation in this illness.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, CIRC 589A, 1719 6th Ave South, Birmingham, AL 25294, USA. Electronic address: jdrummond@uab.edu.
authors.forename: Jana B
authors.initials: JB
authors.lastname: Drummond
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, CIRC 589A, 1719 6th Ave South, Birmingham, AL 25294, USA.
authors.forename: Janusz
authors.initials: J
authors.lastname: Tucholski
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, James J Peters Veteran Administration, Room 4F-20, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, CIRC 589A, 1719 6th Ave South, Birmingham, AL 25294, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Meador-Woodruff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011180:Postmortem Changes; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000473:pathology*
chemical_list: D014150:Antipsychotic Agents; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C413185:TARP; D006220:Haloperidol