The role of iron in inflammatory oligodendrocyte pathology: From clinical to cell culture

• Author / Creator

  Johnson, Erika B

• MS is a chronic demyelinating disease of the CNS that presents with debilitating symptoms in the later stages of disease progression and therefore a high demand for targeted disease-modifying treatments exists. In order to create effective treatments the causalities between the symptoms and pathological mechanisms of the disease need to be properly understood. One such area that remains poorly understood is the role of excess iron deposition in disease aetiology and progression. Literature has shown excess iron deposition in the brains of those with MS. However, whether it is the concentration of excess deposition, the brain-specific regions of deposition, or even the method of iron deposition/metabolism that causes this excess deposition is not understood. This thesis presents a set of experiments that observe the possible role of iron on inflammatory oligodendrocyte pathology, from a macro-to a micro-level. First, the deposition pattern of iron in regards to gross anatomy in brains affected by MS is observed and quantified using MRI images as well as tissue samples. The data presented here suggests that both the severity and/or maturity of the lesion play a role in the level of excess and pattern of iron deposition. Second, a set of experiments are performed that manipulate a pathway crucial to iron homeostasis as well as a group of receptors implicated in the disease progression of MS (HO-1 and P2X respectively) to elucidate possible synergistic activity between them. The results suggest an association between the purinergic receptors and the HO-1 pathway.

• Subjects / Keywords

  • Microglia
  • SnPP
  • Inflammation
  • TR33B
  • Iron
  • Hemin
  • CORM-2
  • Co-culture
  • MRI
  • Multiple sclerosis

• Graduation date

  Spring 2017

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3V698Q76

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.