• Login as Editor
    View Item 
    •   Yeshiva Academic Institutional Repository
    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
    • View Item
    •   Yeshiva Academic Institutional Repository
    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Myelin-specific gene expression in the human fetal spinal cord and the effects of HIV infection and proinflammatory cytokines on developing white matter in vitro

    Thumbnail

    Date
    1996
    Author
    Grever, William Earl
    Metadata
    Show full item record
    Share
    Abstract
    The hypotheses tested in this dissertation are that exposure of the developing human central nervous system (CNS) to human immunodeficiency virus-1 (HIV) and/or proinflammatory cytokines are injurious to oligodendrocytes and disrupt myelin formation. The basis for this hypothesis is the prominence of white matter disease that develops in children with congenital HIV infection. The etiology of HIV associated white matter disease in children is unknown.;We developed a model system to examine the effects of proinflammatory cytokines and HIV on myelination in the developing human. The model consists of cultured transverse sections (slices) of human fetal spinal cord. This culture system maintained the complex architecture of the immature CNS and provided a means to study the interactions of different cell types and how these interactions affect oligodendrocytes and myelin during development.;Spinal cord slices were cultured in one of two formats, non-adherent or adherent. The non-adherent slice cultures allowed for examination of oligodendrocyte gene expression and myelin maintenance in the presence of proinflammatory cytokines and HIV infection of the CNS.;Adherent slice cultures produced an area of outgrowth consisting primarily of oligodendrocytes. These cells were examined for survival and morphological alterations after acute exposure to proinflammatory cytokines.;The results from this research have shown that chronic exposure to proinflammatory cytokines resulted in a decrease in myelin basic protein (MBP) mRNA. However, the ultrastructure of myelin lamellae and the amount of MBP detected in the cultures were unaltered. Acute cytokine exposure or chronic HIV exposure had no effect on oligodendrocytes or myelin.;Astrocytes down-regulated glial fibrillary acidic protein (GFAP) expression due to chronic cytokine exposure and exposure to either heat-inactivated HIV or infectious HIV. Ramified microglia were depleted from the culture after chronic cytokine exposure. Chronic exposure to infectious HIV increased the number of ameboid microglia in the culture.;These results suggest that the etiology of white matter disease associated with HIV encephalopathy is probably a result of indirect mechanisms that involve multiple cell types and chronically elevated levels of inflammatory cytokines.;A characterization of oligodendrocyte-specific gene expression in human fetal spinal cords from 12 to 24 gestational weeks was also documented.
    Permanent Link(s)
    https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9701023
    https://hdl.handle.net/20.500.12202/3687
    Citation
    Source: Dissertation Abstracts International, Volume: 57-08, Section: B, page: 4836.;Advisors: William D. Lyman.
    *This is constructed from limited available data and may be imprecise.
    Collections
    • Albert Einstein College of Medicine: Doctoral Dissertations [1674]

    Yeshiva University Libraries copyright © 2021  DuraSpace
    YAIR Self-Deposit | YAIR User's Guide | Take Down Policy | Contact Us
    Yeshiva University
     

     

    Browse

    AllCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login as Editor

    Statistics

    View Usage Statistics

    Yeshiva University Libraries copyright © 2021  DuraSpace
    YAIR Self-Deposit | YAIR User's Guide | Take Down Policy | Contact Us
    Yeshiva University