The Cellular and Molecular Response of Oligodendroglia to Physical Exercise following Demyelination
Date
2018-05-03
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
While the efficacy of exercise in the management of cardiovascular, lipid, glycemic,
and other systemic disorders has been well documented and long studied, the
beneficial effect of exercise on the central nervous system (CNS) has only recently
gained substantial support from the literature. Exercise has been shown to initiate
pleiotropic mechanisms that increase the functional acuity of many aspects of the
CNS, protect against future pathology, and possibly reverse existing disability. While
there has been significant study of the effect of exercise on the pathophysiology of
neurodegenerative disorders and on general CNS well-being, there has been only
limited study of exercise in demyelinating disorders, such as multiple sclerosis (MS),
particularly with regard to whether exercise promotes reparative processes. In this
thesis I investigate the effect of exercise on the regeneration of myelin in the
lysolecithin model of focal demyelination. I show that exercise enhances
oligodendrogenesis and the formation of myelin, substantially accelerating the
remyelination process. I show that the activation of a transcriptional coactivation,
peroxisome-proliferator activated receptor gamma coactivation 1 alpha (PGC1a), is
enhanced by exercise and required for the acceleration of myelin thickening. I then
show that exercise works in combination with clemastine, resulting in functionally
complete remyelination of lysolecithin lesions. Moreover, the combination
treatment preserves axons. Thus, exercise should have considerable clinical utility
in disorders where demyelination is present. Finally, I detail a novel technique for
visualizing oligodendrocytes in three-dimensions.
Description
Keywords
Demyelination, Remyelination, exercise
Citation
Jensen, S. K. (2018). The Cellular and Molecular Response of Oligodendroglia to Physical Exercise following Demyelination (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/31894