The Effects of Iron Status and Neuroinflamation on Oligodendrocytes : With Implications for Cerebral Malaria
- Author
- Leitner, Dominique
- Published
- [University Park, Pennsylvania] : Pennsylvania State University, 2015.
- Physical Description
- 1 electronic document
- Additional Creators
- Connor, James
Access Online
- etda.libraries.psu.edu , Connect to this object online.
- Graduate Program
- Restrictions on Access
- Open Access.
- Summary
- Iron is an essential cofactor that is necessary for a variety of functions in the brain, including myelination, cell respiration, cell proliferation, and neurotransmitter synthesis. As a result, iron deficiency (ID), which is the most common nutritional disorder in the world, is associated with a variety of functional deficits that can result in long-term neurological impairments. The focus of my thesis is the iron storage protein ferritin and its receptor Tim2 (T cell immunoglobulin and mucin domain containing 2). The Tim2 receptor is expressed by oligodendrocytes in the brain and the interaction between ferritin and the Tim2 receptor is important for iron delivery and differentiation. The thesis begins with an overview of iron homeostasis. In Chapter 2, I provide a background on ID and report the results of rat and cell culture models of ID. In addition to ferritin, Tim2 also interacts with Semaphorin4A (Sema4A), which has been implicated as a cytotoxic agent for oligodendrocytes in multiple sclerosis. We investigated the effect of Sema4A on oligodendrocytes in Chapter 3 and also in a model of neuroinflammatory disease known to have myelin damage, cerebral malaria (CM). We investigated the pathogenesis of CM in mouse models of dietary ID and genetic iron overload (H67D HFE). Our findings give insight into the pathogenesis of CM under varying conditions of iron dyshomeostasis and provide implications for therapeutic strategies in treating ID and CM.In summary, my thesis has shown that 1) Tim2 expression by oligodendrocytes is responsive to changes in iron availability, 2) Sema4A is cytotoxic to oligodendrocytes and elevated in the brain in models of neuroinflammation, and 3) it is possible for iron to be present in normal or even elevated levels without exacerbating CM as long as the inflammatory response to parasitemia is limited.
- Other Subject(s)
- Genre(s)
- Dissertation Note
- Ph.D. Pennsylvania State University, 2015.
- Reproduction Note
- Microfilm (positive). 1 reel ; 35 mm. (University Microfilms 106-75118)
- Technical Details
- The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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