• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Mechanism of hippocampal neuron death in the trisomy 16 mouse: Failure of BDNF signaling

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Find Full text
    Author
    Dorsey, Susan Grace
    Advisor
    Krueger, Bruce K.
    Waltz, Carolyn Feher
    Date
    2001
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Down syndrome (DS; trisomy 21) is the most common genetic cause of mental retardation, affecting about one in every 800 individuals. About 60% of the genes on human chromosome 21 are present on mouse chromosome 16 and mouse trisomy 16 (Ts16) has been studied as a potential model for DS. Cultured hippocampal neurons from embryonic Ts16 mice undergo accelerated death by apoptosis in vitro compared with neurons from Euploid littermates. The purpose of this study was to determine the molecular mechanism underlying this accelerated death. Brain-derived Neurotrophic Factor (BDNF), acting through its receptor, trkB, is a well-described autocrine survival factor for hippocampal neurons. BDNF binding to trkB initiates receptor dimerization, autophosphorylation, and activation of several signaling pathways, including AKT and ERK, two signal transduction molecules whose activation by phosphorylation promotes cell survival. To test whether BDNF promoted autocrine survival in Euploid and Ts16 neuronal cultures, endogenous BDNF was removed from the culture medium using a trkB-IgG fusion protein. In the absence of BDNF, Euploid survival was decreased two- to three-fold, similar to control Ts16 survival levels. Survival of the Ts16 neurons was not affected by the removal of BDNF, indicating an absence of autocrine survival signaling by BDNF. Moreover, unlike Euploid neurons, BDNF did not prevent death induced by serum supplement withdrawal in Ts16 neurons. Both Euploid and Ts16 neurons express full-length, catalytically-active trkB, however Ts16 neurons over-express a truncated, kinase-inactive isoform of trkB, which could act as a dominant negative inhibitor of survival signaling. To test whether the over-expression of truncated trkB in Ts16 neurons was the cause of their inability to respond to BDNF, Ts16 neurons were infected with replication-incompetent adenoviruses containing DNA for full-length trkB. The over-expression of full-length trkB in Ts16 neurons completely restored BDNF-mediated survival signaling. In parallel experiments, the over-expression of truncated trkB in Euploid neurons abolished their responsiveness to BDNF, rendering them indistinguishable from Ts16 control neurons. Thus, Ts16 neurons have a selective BDNF survival defect, probably caused by excess truncated trkB, which can be corrected by increasing the levels of full-length trkB.
    Description
    University of Maryland, Baltimore. Nursing. Ph.D. 2001
    Keyword
    Biology, Neuroscience
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/1202
    Collections
    Theses and Dissertations School of Nursing
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.