Logo for the University of Illinois at Chicago
    • Login
    View Item 
    •   INDIGO Home
    • Medicine, College of
    • College of Medicine at Chicago
    • Psychiatry, Department of
    • Publications - Psychiatry
    • View Item
    •   INDIGO Home
    • Medicine, College of
    • College of Medicine at Chicago
    • Psychiatry, Department of
    • Publications - Psychiatry
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders.

    Thumbnail
    View/Open
    Main Article (2.323Mb)
    Date
    2016-04-05
    Author
    Guidotti, A
    Grayson, DR
    Caruncho, HJ
    Publisher
    Frontiers Media
    Metadata
    Show full item record
    Abstract
    REELIN (RELN) is a large (420 kDa) glycoprotein that in adulthood is mostly synthesized in GABAergic neurons of corticolimbic structures. Upon secretion in the extracellular matrix (ECM), RELN binds to VLDL, APOE2, and α3β2 Integrin receptors located on dendritic shafts and spines of postsynaptic pyramidal neurons. Reduced levels of RELN expression in the adult brain induce cognitive impairment and dendritic spine density deficits. RELN supplementation recovers these deficits suggesting a trophic action for RELN in synaptic plasticity. We and others have shown that altered RELN expression in schizophrenia (SZ) and bipolar (BP) disorder patients is difficult to reconcile with classical Mendelian genetic disorders and it is instead plausible to associate these disorders with altered epigenetic homeostasis. Support for the contribution of altered epigenetic mechanisms in the down-regulation of RELN expression in corticolimbic structures of psychotic patients includes the concomitant increase of DNA-methyltransferases and the increased levels of the methyl donor S-adenosylmethionine (SAM). It is hypothesized that these conditions lead to RELN promoter hypermethylation and a reduction in RELN protein amounts in psychotic patients. The decreased synthesis and release of RELN from GABAergic corticolimbic neurons could serve as a model to elucidate the epigenetic pathophysiological mechanisms acting at pyramidal neuron dendrites that regulate synaptic plasticity and cognition in psychotic and non-psychotic subjects.
    Subject
    Dab1
    RELN
    bipolar disorder
    promoter methylation
    schizophrenia
    synaptic plasticity
    Type
    Article
    Date available in INDIGO
    2016-06-21T16:19:06Z
    URI
    http://hdl.handle.net/10027/20788
    Collections
    • Publications - Psychiatry

    DSpace software copyright © 2002-2015  DuraSpace
    Contact Us | Send Feedback | Privacy Statement
    Theme by 
    Atmire NV

    Browse

    All of INDIGOCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    DSpace software copyright © 2002-2015  DuraSpace
    Contact Us | Send Feedback | Privacy Statement
    Theme by 
    Atmire NV