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    Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression.

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    Authors
    Behan, A T
    Byrne, C
    Dunn, M J
    Cagney, G
    Cotter, D R
    Affiliation
    Department of Psychiatry, Royal College of Surgeons in Ireland, RCSI ERC, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.
    Issue Date
    2009-06
    MeSH
    Adult
    Aged
    Bipolar Disorder
    Blotting, Western
    Cell Adhesion Molecules, Neuronal
    Chromatography, Liquid
    Electrophoresis, Gel, Two-Dimensional
    Electrophoresis, Polyacrylamide Gel
    Female
    GPI-Linked Proteins
    Humans
    Male
    Membrane Proteins
    Middle Aged
    Munc18 Proteins
    Nerve Tissue Proteins
    Prefrontal Cortex
    Proteomics
    Receptors, Transferrin
    Repressor Proteins
    Reproducibility of Results
    Schizophrenia
    Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
    Tandem Mass Spectrometry
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    Citation
    Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression. 2009, 14 (6):601-13 Mol. Psychiatry
    Journal
    Molecular psychiatry
    URI
    http://hdl.handle.net/10147/127686
    DOI
    10.1038/mp.2008.7
    PubMed ID
    18268500
    Abstract
    The dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane microdomains (MM). In the current study, we used two complementary proteomic methods, two-dimensional difference gel electrophoresis and one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by reverse phase-liquid chromatography-tandem mass spectrometry (RP-LC-MS/MS) (gel separation liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)) to assess protein expression in MM in pooled samples of dlpfc from SCZ, BPD and control cases (n=10 per group) from the Stanley Foundation Brain series. We identified 16 proteins altered in one/both disorders using proteomic methods. We selected three proteins with roles in synaptic function (syntaxin-binding protein 1 (STXBP1), brain abundant membrane-attached signal protein 1 (BASP1) and limbic system-associated membrane protein (LAMP)) for validation by western blotting. This revealed significantly increased expression of these proteins in SCZ (STXBP1 (24% difference; P<0.001), BASP1 (40% difference; P<0.05) and LAMP (22% difference; P<0.01)) and BPD (STXBP1 (31% difference; P<0.001), BASP1 (23% difference; P<0.01) and LAMP (20% difference; P<0.01)) in the Stanley brain series (n=20 per group). Further validation in dlpfc from the Harvard brain subseries (n=10 per group) confirmed increased protein expression in SCZ of STXBP1 (18% difference; P<0.0001), BASP1 (14% difference; P<0.0001) but not LAMP (20% difference; P=0.14). No significant differences in STXBP1, BASP1 or LAMP protein expression in BPD dlpfc were observed. This study, through proteomic assessments of MM in dlpfc and validation in two brain series, strongly implicates LAMP, STXBP1 and BASP1 in SCZ and supports the view of a neuritic and synaptic dysfunction in the neuropathology of SCZ.
    Item Type
    Article
    Language
    en
    ISSN
    1476-5578
    ae974a485f413a2113503eed53cd6c53
    10.1038/mp.2008.7
    Scopus Count
    Collections
    Beaumont Hospital

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