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dc.contributor.advisorDoucette, J. Ronalden_US
dc.contributor.advisorNazarali, Adil J.en_US
dc.creatorJiao, Rubinen_US
dc.date.accessioned2010-10-08T15:15:34Zen_US
dc.date.accessioned2013-01-04T05:00:53Z
dc.date.available2011-11-01T08:00:00Zen_US
dc.date.available2013-01-04T05:00:53Z
dc.date.created2010-10en_US
dc.date.issued2010-10en_US
dc.date.submittedOctober 2010en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-10082010-151534en_US
dc.description.abstractDuring 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.en_US
dc.language.isoen_USen_US
dc.subjectoligodendrocyteen_US
dc.subjectagingen_US
dc.subjectmyelinen_US
dc.titleThe effect of aging on myelinating gene expression and oligodendrocyte cell densitiesen_US
thesis.degree.departmentCollege of Pharmacy and Nutritionen_US
thesis.degree.disciplineCollege of Pharmacy and Nutritionen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMaster of Science (M.Sc.)en_US
dc.type.materialtexten_US
dc.type.genreThesisen_US
dc.contributor.committeeMemberMuir, Gillianen_US
dc.contributor.committeeMemberAlcorn, Janeen_US
dc.contributor.committeeMemberCayabyab, Franciscioen_US


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