• Login
    View Item 
    •   UTMB Health SHARED Home
    • Electronic Theses and Dissertations
    • Published ETD Collection
    • View Item
    •   UTMB Health SHARED Home
    • Electronic Theses and Dissertations
    • Published ETD Collection
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Onset of Insulin Resistance in Hippocampal Synapses After Traumatic Brain Injury: Relevance to Alzheimer’s disease and Therapeutic Implications

    Thumbnail
    View/Open
    FRANKLIN-DISSERTATIONDOCTORAL-2019.pdf (4.181Mb)
    Author
    Franklin, Whitney
    Metadata
    Show full item record
    Abstract
    Traumatic brain injury (TBI) is a risk factor for the later development of Alzheimer’s disease (AD), although the mechanisms contributing to this increased risk are unknown. Insulin resistance is an additional risk factor for AD whereby decreased insulin signaling increases synaptic sensitivity to amyloid beta (Aβ) and tau, thus contributing to the cognitive decline that characterizes this neurodegenerative disorder. Considering this, I used male Sprague-Dawley rats that underwent a lateral fluid percussion injury (FPI) at acute (2 and 7 days post-injury), intermediate (28 days post-injury), and chronic (3 months post-injury) time-points to investigate whether decreased insulin responsiveness in TBI animals is playing a role in synaptic vulnerability to AD pathology. I was able to detect acute and chronic decreases in insulin responsiveness in isolated hippocampal synaptosomes after TBI. In addition to assessing both Aβ and tau binding on synaptosomes, I performed electrophysiology at the intermediate and chronic time-points to assess the dysfunctional impact of Aβ and tau oligomers as well as the protective effect of insulin. While I found no difference in binding or degree of LTP inhibition by either Aβ or tau oligomers between sham and TBI animals, I did find that insulin treatment was able to block oligomer-induced LTP inhibition in sham animals but not in TBI animals. Since insulin treatment has been discussed as a therapy for AD, this gives valuable insight into therapeutic implications of treating AD patients based on a patient’s history of associated risk factors.
    URI
    https://hdl.handle.net/2152.3/11320
    Collections
    • Published ETD Collection

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    TDL
    Theme by 
    Atmire NV
     

     

    Browse

    All of UTMB Health SHAREDCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsBy DepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsBy Department

    My Account

    Login

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    TDL
    Theme by 
    Atmire NV