Formation of New Oligodendrocytes in the Spinal Cord Following Macrophage Activation
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The Ohio State University / OhioLINK
2009
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu12614198072021-08-03T05:58:05Z Formation of New Oligodendrocytes in the Spinal Cord Following Macrophage Activation Schonberg, David L. Biology Biomedical Research oligodendrocyte macrophage iron toll-like receptor spinal cord injury neurodegeneration Spinal cord injury (SCI) causes devastating functional deficits including upper and lower limb paralysis, sexual dysfunction, and loss of bladder and bowel control. These problems arise when nerve fibers become damaged, thus preventing information from being transmitted between the brain and the rest of the body. As a result neurons, which process this information, and oligodendrocytes, which enhance conduction of these signals, become vulnerable and undergo cell death. Loss of these cells then leads to further neurological and functional problems. Therefore, replenishing these cell populations in the adult central nervous system (CNS) provides a potential therapy for ultimately improving the lives of injured patients. Cell renewal, particularly of the oligodendrocyte lineage, requires proliferation and maturation of immature cells that can develop into oligodendrocytes. This process can be influenced by activated macrophages, an immune cell that responds to brain and spinal cord pathologies. In addition to releasing a variety of immune-related molecules, macrophages secrete iron and the main iron storage protein, ferritin. Iron is of great importance since it is one of the most tightly regulated elements in the CNS. It can be toxic if its levels are too high yet at the same time is required for a number of critical functions. Iron is necessary for the synthesis of neurotransmitters (dopamine and norepinephrine), oligodendrocyte cell membrane constituents (lipids and cholesterol) and genetic material such as DNA. Since iron is also essential for proper cell cycle regulation, there is a critical need for a complete understanding of its metabolism during oligodendrocyte lineage progression. Activated macrophages can greatly influence iron balance and therefore indirectly affect oligodendrocyte function since these cells need iron for forming myelin wraps around nerve fibers. For instance, macrophages attempt to prevent the spread of bacterial infections by sequestering iron. In addition, activated macrophages can secrete ferritin-bound iron which can be safely internalized by oligodendrocytes and function to promote their survival. Thus, macrophages may contribute to oligodendrocyte survival and renewal by removing potentially toxic amounts of excess iron and then releasing iron in a controlled fashion when it is safely bound to ferritin. Determining the extent to which macrophages regulate iron availability and indirectly contribute to new oligodendrocyte formation is important given the essential role of iron in many physiological functions. Specifically, the experiments discussed in this dissertation reveal that macrophages, depending on how they are activated, can promote oligodendrogenesis and this phenomenom is due in part by iron accumulation in new oligodendrocytes. Furthermore, proving our hypothesis that the source of ferritin comes from activated macrophages which is required for promoting new oligodendrocyte formation would have enormous relevance in CNS diseases where oligodendrocytes are lost (e.g. SCI and multiple sclerosis). 2009 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1261419807 http://rave.ohiolink.edu/etdc/view?acc_num=osu1261419807 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biology Biomedical Research oligodendrocyte macrophage iron toll-like receptor spinal cord injury neurodegeneration |
| spellingShingle |
Biology Biomedical Research oligodendrocyte macrophage iron toll-like receptor spinal cord injury neurodegeneration Schonberg, David L. Formation of New Oligodendrocytes in the Spinal Cord Following Macrophage Activation |
| author |
Schonberg, David L. |
| author_facet |
Schonberg, David L. |
| author_sort |
Schonberg, David L. |
| title |
Formation of New Oligodendrocytes in the Spinal Cord Following Macrophage Activation |
| title_short |
Formation of New Oligodendrocytes in the Spinal Cord Following Macrophage Activation |
| title_full |
Formation of New Oligodendrocytes in the Spinal Cord Following Macrophage Activation |
| title_fullStr |
Formation of New Oligodendrocytes in the Spinal Cord Following Macrophage Activation |
| title_full_unstemmed |
Formation of New Oligodendrocytes in the Spinal Cord Following Macrophage Activation |
| title_sort |
formation of new oligodendrocytes in the spinal cord following macrophage activation |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2009 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1261419807 |
| work_keys_str_mv |
AT schonbergdavidl formationofnewoligodendrocytesinthespinalcordfollowingmacrophageactivation |
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1719428598158327808 |