LE3 .A278 2018

2018

Wilson, Brian

Acadia University

Bachelor of Science

Honours

Biology

Biology

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the Central Nervous System (CNS) for which there is currently no cure. Pioglitazone is a PPAR-y agonist approved by the FDA for the treatment of type 2 diabetes. Pioglitazone has been shown to reduce disease severity in a systemic mouse model of MS (Experimental Autoimmune Encephalomyelitis; EAE) and has exhibited anti-inflammatory properties in a number of in vitro studies, suggesting it may be capable of promoting remyelination in MS. This study aims to fill the void that exists in restorative treatment options for MS by investigating the effects of pioglitazone in a mouse model of focal demyelination. Mice received a stereotactic injection of the toxin lysolecithin (LPC) into one side of the corpus callosum and PBS into the other side. Mice received either vehicle or pioglitazone by oral gavage once daily for seven days beginning one day post-injection. After seven days, demyelination within the corpus callosum was measured using histology; macrophage/microglia activation within demyelinated lesions was measured using Immunohistochemistry (IHC). Both LPC lesion volumes and microglial activation in mice treated with pioglitazone were found to be greater, on average, relative to LPC lesion volumes and microglial activation in mice treated with vehicle. However, neither of these differences were statistically significant. Given the ability of the LPC model to study remyelination in relative isolation, pioglitazone is likely not effective in directly promoting remyelination. Findings from this study thus suggest that pioglitazone may reduce disease severity in the EAE model through modulating the immune system. More research is needed in this area in order to confirm pioglitazone’s mechanism of action.

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https://scholar.acadiau.ca/islandora/object/theses:2619