UBC Theses and Dissertations
Quantifying iron levels in the YAC128 mouse model of Huntington's Disease Muller, Michelle
Huntington's Disease (HD) is one of many neurodegenerative diseases with reported alterations in brain iron homeostasis. Many neurodegenerative diseases exist which are characterized by brain iron accumulation. Whether elevated brain iron occurs in HD, and whether it plays a significant contributory role in pathogenesis or is a secondary effect is currently unclear. Iron accumulation in specific brain areas of neurodegeneration in HD has been proposed based on observations in post-mortem tissue and magnetic resonance imaging (MRI) studies. Altered MRI signal within specific brain regions undergoing neurodegeneration has been consistently reported and interpreted as altered levels of brain iron. Biochemical studies using various techniques to measure iron species in human samples, mouse tissue, or in vitro has generated equivocal data to support such an association. I have reviewed previous and current published literature reporting iron alterations and summarized the findings in this dissertation. Current consensus remains unclear if iron plays a contributing role, and further studies that modulate iron levels in HD models to assess the effects of iron are required. The experimental aim of this thesis was to measure iron-related changes in the YAC128 HD mouse model with the hypothesis that this mouse model will develop elevated striatal iron levels compared with wild-type littermates. Using analytical techniques to measure levels of elemental brain iron, no significant differences were observed in various brain regions of aged HD mice and in post-mortem HD samples.
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