Barrett

Barrett, The Honors College at Arizona State University proudly showcases the work of undergraduate honors students by sharing this collection exclusively with the ASU community.

Barrett accepts high performing, academically engaged undergraduate students and works with them in collaboration with all of the other academic units at Arizona State University. All Barrett students complete a thesis or creative project which is an opportunity to explore an intellectual interest and produce an original piece of scholarly research. The thesis or creative project is supervised and defended in front of a faculty committee. Students are able to engage with professors who are nationally recognized in their fields and committed to working with honors students. Completing a Barrett thesis or creative project is an opportunity for undergraduate honors students to contribute to the ASU academic community in a meaningful way.

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Using Transgenic Mice (APP/PS1) to Model Alzheimer’s Disease to Understand Hippocampal-Dependent Memory

Description

Alzheimer’s disease (AD) is an irreversible brain disorder that plagues millions of people with no current cure. Current clinical research is slowly advancing to more definitive treatments in hopes of reducing the effects of progressive cognitive and behavioral decline, but none so far can slow AD’s onset. A brain area…

Alzheimer’s disease (AD) is an irreversible brain disorder that plagues millions of people with no current cure. Current clinical research is slowly advancing to more definitive treatments in hopes of reducing the effects of progressive cognitive and behavioral decline, but none so far can slow AD’s onset. A brain area known as the nucleus incertus (NI) was recently discovered to potentially impact AD because of its connections to brain targets that degenerate; however, the NI’s role is unknown. This goal of this experiment was to use a transgenic mouse model (APP/PS1) that expresses AD pathology slowly as found in humans, and to test the mice in a variety of cognitive and anxiety assessments. Mice of both sexes and two different ages were used, with the first being young adult before AD pathology manifests (around 3-4 months old), and the second being around the cusp of when AD pathology manifests (late adult, 8-10 months old). The mice were tested in a variety of cognitive tasks that included the novel object recognition (NOR), Morris water maze (MWM), and the object placement (OP), with the latter being the focus of my thesis. Anxiety measures were taken from the open field (OF) and elevated plus maze (EPM) with the visible platform (VP) used to ensure mice could perform on the rigorous MWM task. In the OP, we found an age effect, where the older mice were less likely to explore the moved object during the OP compared to the younger mice; motor ability was unlikely to explain this effect. We did not find any significant age by genotype effects. These findings indicate that cognitive impairment only just started to affect the older cohort, since OP impairment was found on one measure and not another. Other measures currently being quantified will be helpful in understanding this data, and to see whether learning, memory, and anxiety are affected.
ContributorsDapon, Bianca (Author) / Conrad, Cheryl (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2023-05

Investigating Whether Early Stage Memory Impairment Can be Detected in a Mouse Model of Alzheimer’s Disease

Description
Alzheimer’s disease (AD) is characterized by memory decline and dementia, and conclusively diagnosed postmortem from tangles and plaques. Plaques come from β-amyloid protein (Aβ), which damages the brain, especially the hippocampus, a structure vital for memory formation. However, whether plaques and tangles cause or result from AD is unclear. Our…

Alzheimer’s disease (AD) is characterized by memory decline and dementia, and conclusively diagnosed postmortem from tangles and plaques. Plaques come from β-amyloid protein (Aβ), which damages the brain, especially the hippocampus, a structure vital for memory formation. However, whether plaques and tangles cause or result from AD is unclear. Our goal was to use a preclinical AD model to identify the early stages of cognitive dysfunction before AD becomes severe to enhance targeted interventions. We used a transgenic mouse (APP/PS1) that slowly develops plaques, with minimal expression around 5-6 months (young adult) with more expression by 12 months (middle-age). Our aim was to determine whether young adult mice would show cognitive symptomatology that could be used as a future metric for targeted treatment before AD advances further. We had three independent variables: Sex (Male, Female), Age (5-6, 8-10 months) and Genotype (APP/PS1, wildtype, WT). We used behavioral assays to assess spatial memory (hippocampal function), working memory (prefrontal cortex function), and anxiety (amygdala function). For my honor’s thesis, I focused on using the Morris Water Maze (MWM) to assess hippocampal function and the Open Field (OF) to assess anxiety and locomotion. In MWM, all groups were given four trials/day for four days with a probe trial to assess strategy immediately after the last trial on day 4. All groups swam shorter distances across days to show they were learning and revealed sex differences. The APP/PS1 males (young and old) learned the task more slowly than their WT male counterparts, but were using spatial strategies as demonstrated by the probe trial. For the females, all groups learned the task similarly, but the probe trial revealed that the APP/PS1 females (young and old) were using non-spatial strategies. Moreover, the males significantly swam shorter distances than the females, learning faster. The use of the visible platform task confirmed that the mice were capable of performing the swim task. For the OF, mice were placed in a square arena and given 10 minutes to explore and found sex differences in anxiety profile. All the female mice expressed similar anxiety profiles, whereas the APP/PS1 males had higher anxiety profiles than their WT males counterparts. These results revealed that there were sex-specific differences in cognition and anxiety profiles in the APP/PS1 mouse model. This indicates that individual characteristics are important to consider when using tailored interventions. In summary, these findings emphasize the potential for early detection and targeted treatment strategies to help mitigate AD progression.
ContributorsMontero, Martina Anne (Author) / Conrad, Cheryl (Thesis director) / Gewirtz, Jonathan (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2024-05