Identifying the mechanism of aged oligodendrocyte progenitor cell rejuvenation by young cerebrospinal fluid
Abstract/Contents
- Abstract
- As humans age and develop aging-related diseases, many learning and memory functions can be compromised as the myelin sheath surrounding axons is lost. Previous work has demonstrated that these cognitive functions, which are mainly coordinated in the hippocampus, require the activity-dependent myelination of axons by oligodendrocytes. Given the literature demonstrating myelin degeneration with aging and neurodegenerative disease, we hypothesized that loss of white matter could drive aging-related cognitive decline and that protecting myelin could prevent this decline. This project aims to characterize the effects of exposing aged mice to young mouse cerebrospinal fluid (CSF) and identify the mechanism of oligodendrocyte rejuvenation. The paradigm for this project involved extracting CSF from young mice and transfusing it to aged mice through carefully regulated mini-osmotic pumps. These mice were then used for behavioral studies, immunohistochemistry staining, and sequencing experiments. The results showed increased proliferation and differentiation of aged oligodendrocyte progenitor cells (OPCs) when exposed to young CSF. Further characterization of transcriptomic changes revealed the upregulation of a few transcriptional factors including serum response factor (SRF) which is known to play an important regulatory role in the contraction of muscle cells. Increased expression of these transcription factors and their downstream targets suggest an actin-mediating mechanism for the rejuvenating effects of young CSF. These findings suggest therapeutics targeting SRF and actin pathways in OPCs could rescue myelination and improve cognitive function in aged mice. Developing therapeutics with these abilities could allow for clinical improvements in learning and memory for the growing elderly population, especially those suffering from aging-related memory disorders.
Description
| Type of resource | text |
|---|---|
| Date created | June 2021 |
| Date modified | December 5, 2022 |
| Publication date | May 3, 2022 |
Creators/Contributors
| Author | Myneni, Saket |
|---|---|
| Degree granting institution | Stanford University, Department of Biology, 2021 |
| Thesis advisor | Wyss-Coray, Tony |
| Thesis advisor | McConnell, Susan |
Subjects
| Subject | Biology |
|---|---|
| Subject | Aging |
| Subject | Myelin |
| Subject | Actin |
| Subject | Activity-Dependent |
| Subject | SRF |
| Subject | CSF |
| 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
Myneni, Saket and Wyss-Coray, Tony and McConnell, Susan. (2021). Identifying the mechanism of aged oligodendrocyte progenitor cell
rejuvenation by young cerebrospinal fluid. Stanford Digital Repository. Available at: https://purl.stanford.edu/zc310rm3119
Collection
Undergraduate Theses, Department of Biology, 2020-2021
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- skmyneni@stanford.edu
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