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Neuroprotective Effects of Pramlintide Against Oxidative Stress and Alzheimer's Disease

Patrick, Sarah A
http://orcid.org/0000-0003-1949-9895
http://rave.ohiolink.edu/etdc/view?acc_num=kent1524145067277978

Abstract Details

2018, MS, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and has been intimately linked with Type 2 diabetes mellitus, oxidative stress, and mitochondrial dysfunction. Pramlintide (PRAM), a synthetic analog of amylin, has been used in treatment of diabetes and has shown cognitive benefits in nontransgenic and transgenic mouse models of aging and AD. Due to these connections, we administered PRAM to a new transgenic model (APP/PS1) and hypothesized that PRAM is conferring benefits through the regulation of oxidative stress. Mice treated with 6 µg/day for 120 days showed amelioration of cognitive deficits in Morris Water Maze testing and decreased amyloid-beta plaque burden in the hippocampus. Western blot analysis demonstrated upregulation of endogenous antioxidant enzymes, including MnSOD and glutathione peroxidase 1, in the cortex and hippocampus. In vitro, differentiated NS-1 and SHSY5Y cells showed decreases in oxidative stress as measured by DCF and TBARS assays when treated with PRAM for one hour prior to an oxidative insult. Finally, in differentiated NS-1 cells, PRAM was found to significantly increase levels of reduced glutathione in a dose-dependent fashion. Together, these results indicate that PRAM’s benefits on cognitive function are at least partially related to its ability to reduce oxidative stress.
Gemma Casadesus, PhD (Advisor)
Eric Mintz, PhD (Committee Member)
Colleen Novak, PhD (Committee Member)
95 p.
Neurosciences
oxidative stress, Alzheimers Disease, antioxidants, MnSOD, Glutathione, Glutathione Peroxidase 1, Catalase, amylin, pramlintide

Recommended Citations

Citations

  • Patrick, S. A. (2018). Neuroprotective Effects of Pramlintide Against Oxidative Stress and Alzheimer's Disease [Master's thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1524145067277978

    APA Style (7th edition)

  • Patrick, Sarah. Neuroprotective Effects of Pramlintide Against Oxidative Stress and Alzheimer's Disease . 2018. Kent State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1524145067277978.

    MLA Style (8th edition)

  • Patrick, Sarah. "Neuroprotective Effects of Pramlintide Against Oxidative Stress and Alzheimer's Disease ." Master's thesis, Kent State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1524145067277978

    Chicago Manual of Style (17th edition)

kent1524145067277978
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© 2018, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.