During aging, there is a decrease both in the stability of central nervous system (CNS)
myelin once formed and in the efficiency of its repair by oligodendrocytes (OLs). To
study CNS remyelination during aging, I used the cuprizone (a copper chelator) mouse
model. Inclusion of cuprizone in the diet kills mature OLs and demyelinates axons in the
rostral corpus callosum (RCC) of mice, which enabled me to characterize age-related
changes (i.e., 2-16 months of age) in glial cell response during the recruitment (i.e.,
demyelination) and differentiation (i.e., remyelination) phases of myelin repair. I found
that the time between 12 and 16 months of age is a critical period during which there is
an age-related decrease in the number of OL lineage cells (Olig2Nuc+ve/GFAP-ve cells)
in the RCC of both control mice and mice recovering from cuprizone-induced
demyelination. My results also show there was an age-related impaired recruitment of
progenitor cells to replace lost OLs even though there was no major age-related decrease
in the size of the progenitor cell pool (PDGF á R+ve/GFAP-ve, and
Olig2Nuc+ve/PDGFáR+ve cells). However, there were cuprizone-induced increased
numbers of astrocyte progenitor cells (Olig2Cyto+ve/PDGFáR+ve) in these same mice;
thus PDGFáR+ve progenitor cells in mice as old as 16 months of age retain the ability to
differentiate into astrocytes, with this fate choice occurring following cytoplasmic
translocation of Olig2. These data reveal for the first time age-related differences in the
differentiation of PDGFáR+ve progenitor cells into OLs and astrocytes and lead me to
suggest that during aging there must be a transcriptional switch mechanism in the
progenitor cell fate choice in favour of astrocytes. This may at least partially explain the
age-related decrease in efficiency of OL myelination and remyelination.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-10082010-151534 |
| Date | 01 November 2010 |
| Creators | Jiao, Rubin |
| Contributors | Muir, Gillian, Doucette, J. Ronald, Nazarali, Adil J., Alcorn, Jane, Cayabyab, Franciscio |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-10082010-151534/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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