The Role of the Circadian Clock in Myelin-Forming Cells in Health and Disease
Abstract/Contents
- Abstract
- Myelin is integral to neural circuit function. Nearly half of the human brain is composed of white matter tracts, all of which are created by oligodendrocytes. Oligodendrocyte precursor cells (OPCs), the precursor cell population that gives rise to myelinating oligodendrocytes, are critical in maintaining oligodendrocyte homeostasis. OPCs are the most robustly cycling cell in the brain, yet the mechanisms maintaining this stability remain incompletely understood. One mechanism closely interconnected with cell cycle regulation is the circadian clock. At the cellular level, circadian rhythms are generated ubiquitously throughout the brain and body by a transcriptional/translational feedback loop driven by the transcription factor BMAL1. This thesis elevates the current biological understanding of myelin processes through novel convergence with circadian biology. Specifically, the role of circadian regulation in developmental myelination is investigated by genetic knockout of Bmal1 specifically in OPCs during developmental myelination. OPC and mature oligodendrocyte density is reduced by ~40% in OPC-specific Bmal1 knockout (Bmal1 KO) mice compared to circadian intact OPCs in wild type (Bmal1 WT) mice at postnatal day 21 (P21). Bmal1 KO mice exhibit an ~7% decrease in myelin sheath thickness and ~40% decrease in myelin basic protein (MBP) content, a protein integral to the formation of compact myelin. These deficits in OPC lineage dynamics and myelin are associated with a significant dysregulation of motor and cognitive function exemplified by decrements in limb swing speed and stride length at P35 and deficits in cognition at P63 as assessed using a modified novel object recognition test. Taken together, these data suggest a significant role for the circadian clock protein BMAL1 in the regulation of myelination and a novel avenue by which to evaluate neurological disease..
Description
| Type of resource | text |
|---|---|
| Date created | June 2021 |
| Date modified | December 5, 2022 |
| Publication date | April 25, 2022 |
Creators/Contributors
| Author | Greene, Jacob |
|---|---|
| Contributor | Kim, Samuel |
| Degree granting institution | Stanford University, Department of Biology, 2021 |
| Thesis advisor | Kopito, Ron |
| Thesis advisor | Gibson, Erin |
Subjects
| Subject | circadian rhythm |
|---|---|
| Subject | oligodendrocyte |
| Subject | myelin |
| Subject | neurological disease |
| Subject | Stanford Department of Biology |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
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- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
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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
- Greene, J., Kim, S., Kopito, R. and Gibson, E. (2021). The Role of the Circadian Clock in Myelin-Forming Cells in Health and Disease. Stanford Digital Repository. Available at: https://purl.stanford.edu/ct708yx6831
Collection
Undergraduate Theses, Department of Biology, 2020-2021
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- greene12@stanford.edu
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