Theses and dissertations

This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students. 

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Elucidating the Effects of PRAS40 on Learning and Memory

Description
The mammalian target of rapamycin (mTOR) is integral in regulating cell growth as it maintains a homeostatic balance of proteins by modulating their synthesis and degradation. In the brain, mTOR regulates protein-driven neuroplastic changes that modulate learning and memory. Nevertheless, upregulation of mTOR can cause detrimental effect in spatial memory…

The mammalian target of rapamycin (mTOR) is integral in regulating cell growth as it maintains a homeostatic balance of proteins by modulating their synthesis and degradation. In the brain, mTOR regulates protein-driven neuroplastic changes that modulate learning and memory. Nevertheless, upregulation of mTOR can cause detrimental effect in spatial memory and synaptic plasticity. The proline-rich Akt-substrate 40 kDa (PRAS40) is a key negative regulator of mTOR, as it binds mTOR and directly reduces its activity. To investigate the role of PRAS40 on learning and memory, we generated a transgenic mouse model in which we used the tetracycline-off system to regulate the expression of PRAS40 specifically in neurons of the hippocampus. After induction, we found that mice overexpressing PRAS40 performed better than control mice in the Morris Water Maze behavioral test. We further show that the improvement in memory was associated with a decrease in mTOR signaling, an increase in dendritic spines in hippocampal pyramidal neurons, and an increase in the levels of brain-derived neurotrophic factor (BDNF), a neurotrophin necessary for learning and memory. This is the first evidence that shows that increasing PRAS40 in the mouse brain enhances learning and memory deficits.
ContributorsSarette, Patrick William (Author) / Oddo, Salvatore (Thesis director) / Caccamo, Antonella (Committee member) / Kelleher, Raymond (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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An Evaluation of the Cognitive Effects of a Short-Term and a Long-Term Ovarian Hormone Deprivation in a Transgenic Mouse Model of Alzheimer's Disease: Addressing the Critical Window

Description
With no known cure, Alzheimer's disease (AD) is the most common dementia, affecting more than 5.5 million Americans. Research has shown that women who undergo surgical menopause (i.e. removal of the ovaries) before the onset of natural menopause are at a greater risk for AD. It is hypothesized that this…

With no known cure, Alzheimer's disease (AD) is the most common dementia, affecting more than 5.5 million Americans. Research has shown that women who undergo surgical menopause (i.e. removal of the ovaries) before the onset of natural menopause are at a greater risk for AD. It is hypothesized that this greater relative risk of developing AD is linked to ovarian hormone deprivation associated with surgical menopause. The purpose of these studies was to evaluate the behavioral changes that occur after a short-term (ST) and a long-term (LT) ovarian hormone deprivation in a mouse model of AD. Wildtype (Wt) or APP/PS1 (Tg) mutation mice underwent either a sham surgery or an ovariectomy (Ovx) surgery at three months of age. Study 1 consisted of a short-term cohort that was behaviorally tested one month following surgery on a battery of spatial memory tasks including, the Morris water maze, delayed matched-to-sample water maze, and visible platform task. Study 2 consisted of a long-term cohort that was behaviorally tested on the same cognitive battery three months following surgery. Results of Study 1 revealed that genotype interacted with surgical menopause status, such that after a short-term ovarian hormone deprivation, Ovx induced a genotype effect while Sham surgery did not. Results of Study 2 showed a similar pattern of effects, with a comparable interaction between genotypes and surgical menopause status. These findings indicate that the cognitive impact of ovarian hormone deprivation depends on AD-related genotype. Neuropathology evaluations in these mice will be done in the near future and will allow us to test relations between surgical menopause status, cognition, and AD-like neuropathology.
ContributorsPalmer, Justin M. (Author) / Bimonte-Nelson, Heather (Thesis director) / Oddo, Salvatore (Committee member) / Davis, Mary (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12