MicroRNA-146a: a potential therapeutic target in multiple sclerosis

Snelgrove, Andrew Michael Graham (2018) MicroRNA-146a: a potential therapeutic target in multiple sclerosis. Masters thesis, Memorial University of Newfoundland.

[img] [English] PDF - Accepted Version
Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.

Download (94MB)


Multiple sclerosis (MS) is a neuroinflammatory disease characterized by demyelinated neurons in the central nervous system. Decreased levels of the anti-inflammatory microRNA-146a have previously been observed in macrophages/microglia in MS patients compared to controls. Therapeutically elevating microRNA-146a expression in MS may produce a conducive environment for remyelination. Inflammatory cytokines were assessed from both primary mouse and human macrophages and microglia, and THP-1 macrophages that were transfected with a microRNA-146a mimic and polarized towards a pro-inflammatory phenotype. Inflammatory cytokines and MS-relevant targets were measured following activation; neuro- and oligodendrogenesis were also assessed in vitro while the effect of microRNA-146a on myelin phagocytosis was also examined. MicroRNA-146a may decrease pro-inflammatory TNF but may have little to no effect on IL-6; RhoA may decrease in both mouse and human macrophages. MicroRNA-146a increased myelin phagocytosis of unstimulated primary mouse microglia. Finally, in vitro experiments suggest that supernatants collected from LPS-stimulated murine macrophages transfected with a microRNA-146a mimic do not affect neurogenesis or oligodendrogenesis. It is suggested that increasing microRNA-146a may promote an anti-inflammatory environment beneficial for promoting remyelination in MS.

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/13238
Item ID: 13238
Additional Information: Includes bibliographical references (pages 112-159).
Keywords: multiple sclerosis; microRNA-146a; macrophage; microglia; remyelination; neurogenesis; oligodendrogenesis
Department(s): Medicine, Faculty of > Biomedical Sciences
Date: May 2018
Date Type: Submission
Medical Subject Heading: Multiple Sclerosis; MicroRNAs--therapeutic use; Remyelination.

Actions (login required)

View Item View Item


Downloads per month over the past year

View more statistics