• About
    • Login
    View Item 
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Institutional RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Genetic and functional interactions between Itgb3 and Slc6a4 in mouse brain

    Whyte, Alonzo J.
    : https://etd.library.vanderbilt.edu/etd-03212013-135948
    http://hdl.handle.net/1803/10991
    : 2013-03-29

    Abstract

    In the brain, serotonin (5-hydroxtryptamine, 5-HT) is synthesized in the raphe nucleus. Raphe serotonergic projections modulate neurotransmissions throughout the brain influencing mood and behavior. The serotonin transporter (SERT; SLC6A4) clears 5-HT from the synapse for degradation or reuse, thus regulating levels of 5-HT and limiting its actions on 5-HT receptors. Dysfunction in 5-HT modulation of neurotransmission is associated with mood and developmental disorders including anxiety, depression, and autism and there is genetic evidence for increased risk for depression in individuals possessing polymorphisms in SLC6A4 as well as genes which interact with SLC6A4. ITGB3 encodes integrin β3, a cell adhesion molecule which has been implicated as a modulator of peripheral serotonergic systems via genetic and functional interactions with SLC6A4, as well as in regulation of synaptic plasticity and maturation. In the brain, integrin β3 couples to integrin αv to form a functional receptor, making integrin αvβ3 an interesting target for regulation of neural 5-HT systems. Immunohistochemical experiments revealed integrin β3 localization in serotonergic neurons, colocalized with SERT. Examination of genetic interactions utilizing an Itgb3-/+ x Slc6a4-/+ mouse model revealed reduced SERT expression, and an anxiety- and depression-like phenotype compared to wildtype littermates. Further experimentation of the functional interaction between integrin αvβ3 and SERT via pharmacological targeting of integrin αvβ3 revealed integrin αvβ3 regulation of SERT uptake activity. These studies highlight integrin β3 as a potential modulator of brain 5-HT systems and subsequently 5-HT mediated behavioral phenotypes.
    Show full item record

    Files in this item

    Icon
    Name:
    AlonzoWhyteThesis.pdf
    Size:
    1.338Mb
    Format:
    PDF
    View/Open

    This item appears in the following collection(s):

    • Electronic Theses and Dissertations

    Connect with Vanderbilt Libraries

    Your Vanderbilt

    • Alumni
    • Current Students
    • Faculty & Staff
    • International Students
    • Media
    • Parents & Family
    • Prospective Students
    • Researchers
    • Sports Fans
    • Visitors & Neighbors

    Support the Jean and Alexander Heard Libraries

    Support the Library...Give Now

    Gifts to the Libraries support the learning and research needs of the entire Vanderbilt community. Learn more about giving to the Libraries.

    Become a Friend of the Libraries

    Quick Links

    • Hours
    • About
    • Employment
    • Staff Directory
    • Accessibility Services
    • Contact
    • Vanderbilt Home
    • Privacy Policy