Investigating Prodromal Spine Density in an Alzheimer’s Disease Mouse Model
Abstract/Contents
- Abstract
- Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized clinically by a decline in cognitive function and memory and at the neuropathological level by extracellular deposits of beta amyloid (Aβ) and intercellular neurofibrillary tau tangles. Although Alzheimer’s disease is thought of as a disease of old age, the failure of treatments administered after clinical presentation, as well as research uncovering early neural plasticity changes in mouse models of AD, has ignited interest in understanding prodromal Alzheimer’s disease. APP/PS1 Alzheimer’s disease model mice have deficient ocular dominance plasticity at 30 days of age, which can be prevented if PirB, an innate immune system receptor present in the brain, is knocked out. In addition, synaptic changes correlate with and appear to underlie cognitive dysfunction and behavioral deficits in AD; however, current spine density analyses have focused on aging mice that already have plaques, spine and synapse loss, and significant cognitive deficits. In this project, dendritic spines on layer 5 cortical pyramidal neurons were counted in APP/PS1 mice at one and six months of age to assess the impact of Aβ oligomers early in prodromal Alzheimer’s disease. At 30 days of age, we did not anticipate changes in spine density, as ocular dominance plasticity is the only known plasticity perturbation at this age. At 180 days, we expected to see a decrease in spine density, since plaques begin to form around 6 months of age and deficits in cognition and memory emerge following the appearance of widespread plaques. At 30 days of age, we observed a trend towards lower spine density in PirBWT APP/PS1(+) animals as compared to their APP/PS1(-) counterparts, consistent with their deficient ocular dominance plasticity. Results also indicated that spine density was not greater in PirB knock out (KO) mice as compared to PirBWT mice at 30 days of age. This was unexpected given the previous research indicating that knocking out PirB increases spine density in a variety of ages and may have resulted from low quality images. At 180 days, spine density was greater in PirBKO animals as compared to PirBWT, the expected phenotype. In addition, there was a trend towards greater spine density in the PirBWT APP/PS1(+) animals vs APP/PS1(-) animals. This result was unexpected but could coincide with observations of increased spine turnover and excitability in APP/PS1 mice around 3-6 months of age. Although these results are promising, the inability to replicate expected results at P30 call for further investigation in a full cohort of re-imaged mice at higher resolution, especially at P30, in order to draw firm conclusions about spine density in APP/PS1 mice in the context of PirB.
Description
| Type of resource | text |
|---|---|
| Date created | June 2021 |
| Date modified | December 5, 2022 |
| Publication date | May 4, 2022 |
Creators/Contributors
| Author | LeBlanc, Katherine R. |
|---|---|
| Degree granting institution | Stanford University, Department of Biology, 2021 |
| Thesis advisor | Shatz, Carla J. |
| Thesis advisor | Heller, H. Craig |
Subjects
| Subject | Biology |
|---|---|
| Subject | Alzheimer’s Disease |
| Subject | PirB |
| Subject | prodromal |
| Subject | spine density |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
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- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
Preferred citation
- Preferred citation
- LeBlanc, Katherine R., Shatz, Carla J., and Heller, H. Craig. (2021). Investigating Prodromal Spine Density in an Alzheimer’s Disease Mouse Model. Stanford Digital Repository. Available at: https://purl.stanford.edu/yv889ns5054
Collection
Undergraduate Theses, Department of Biology, 2020-2021
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- kleblanc@stanford.edu
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