Expression of the ionotropic glutamate receptor subunits and NMDA receptor-associated intracellular proteins in the substantia nigra in schizophrenia.

Abstract	Multiple neurotransmitter systems have been implicated in the pathophysiology of schizophrenia. Dopamine hyperactivity has often been implicated in this illness. More recently, the glutamate hypothesis of schizophrenia suggests that NMDA receptor (NMDAR) hypofunction may also play a role in this illness. This is based primarily on studies showing that phencyclidine, an NMDAR antagonist, can induce a schizophreniform psychosis. While NMDAR dysfunction is most often implicated in schizophrenia, other components of the glutamate system, such as the AMPA and kainate receptors, as well as NMDAR-associated intracellular proteins, may also play a role in regulating NMDA receptor activity and glutamate neurotransmission. There is growing interest in the hypothesis that the pathophysiology of schizophrenia involves alterations in dopamine-glutamate interactions. The glutamate system is anatomically and functionally linked to the dopamine system, and glutamate can modulate dopaminergic activity and release by stimulating various glutamate receptor subtypes expressed by dopaminergic neurons in the substantia nigra/ventral tegmental area. In this study, we investigated dopamine-glutamate interactions by measuring the expression of transcripts encoding the subunits for the ionotropic glutamate receptors (NMDA, AMPA and kainate) and five NMDAR-associated intracellular proteins, PSD-93, PSD-95, SAP102, NF-L and yotiao in the dopaminergic neurons in the substantia nigra pars compacta (SNc) of subjects with schizophrenia and a comparison group. Tyrosine hydroxylase (TH, a marker of dopamine-synthesizing cells), NR1 (an NMDA receptor subunit) and GluR5 (a kainate subunit) transcript levels were significantly increased in the SNc in schizophrenia. These data support the hypothesis that schizophrenia may involve alterations in dopamine-glutamate interactions.
Authors	Helena T Mueller, Vahram Haroutunian, Kenneth L Davis, James H Meador-Woodruff
Journal	Brain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 121 Issue 1-2 Pg. 60-9 (Feb 05 2004) ISSN: 0169-328X [Print] Netherlands
PMID	14969737 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	A Kinase Anchor Proteins AKAP9 protein, human Adaptor Proteins, Signal Transducing Akap9 protein, rat Carrier Proteins Cytoskeletal Proteins DLG3 protein, human Disks Large Homolog 4 Protein Dlg4 protein, rat Intracellular Signaling Peptides and Proteins Membrane Proteins Mpp2 protein, rat Nerve Tissue Proteins Neurofilament Proteins Neuropeptides Nuclear Proteins Protein Subunits Receptors, Glutamate Transcription Factors neurofilament protein L postsynaptic density proteins Tyrosine 3-Monooxygenase
Topics	A Kinase Anchor Proteins Adaptor Proteins, Signal Transducing Aged Aged, 80 and over Carrier Proteins (genetics, metabolism) Case-Control Studies Cytoskeletal Proteins (genetics, metabolism) Disks Large Homolog 4 Protein Female Humans In Situ Hybridization (methods) Intracellular Signaling Peptides and Proteins Male Membrane Proteins Middle Aged Nerve Tissue Proteins (genetics, metabolism) Neurofilament Proteins (genetics, metabolism) Neurons (metabolism) Neuropeptides (genetics, metabolism) Nuclear Proteins Protein Subunits (metabolism) Receptors, Glutamate (classification, genetics, metabolism) Schizophrenia (genetics, metabolism) Substantia Nigra (cytology, metabolism) Transcription Factors Tyrosine 3-Monooxygenase (genetics)

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