Increased expression of cytokines and chemokines in the central nervous system (CNS) is closely associated with the development of retroviral-induced neurological diseases such as HIV-associated dementia, as well as other neuropathologies such as Alzheimers Disease and Multiple Sclerosis. The specific functions of many of these pro-inflammatory factors have yet to be elucidated in the disease process, and it is unclear whether the nature of their effects is protective, pathogenic, or both. Additionally, current models of chemokine function have inherent limitations, with direct injection resulting in a brief response that doesnt accurately represent the effects of chronic production, and transgenic mice constitutively expressing chemokines by a large percentage of intrinsic brain cells from inception. This study takes the first step in developing a more representative in vivo system by which the direct of effects of the over-expression of individual CNS chemokines may be studied. C17.2 neural stem cells (NSC) were transduced with retroviral vectors containing the genes for CCL2, CCL7, CCL12, or the vector alone, and were inoculated into mice to generate a more accurate representation of the limited chemokine producing cell population that is seen with disease. The in vivo data generated herein suggests that this system is capable of consistently expressing comparable levels of these three chemokines, and characterizes the migration patterns of these cells into the major regions of the CNS. As no significant glial activation was seen concurrent with CCL over-expression, this study provides support for idea that the CCL chemokines may be involved in priming the CNS immune response, rather than its direct initiation. Additionally, ancillary histopathological data suggests a possible role for CCL12 in the development of spongiform lesions in the presence of recombinant retrovirus infection.
| Identifer | oai:union.ndltd.org:LSU/oai:etd.lsu.edu:etd-11172005-185717 |
| Date | 22 November 2005 |
| Creators | Stalder, Mark Winston |
| Contributors | Marlene S. Orandle, K. Gus Kousoulas, Karin E. Peterson |
| Publisher | LSU |
| Source Sets | Louisiana State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lsu.edu/docs/available/etd-11172005-185717/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached herein a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to LSU or its agents the non-exclusive license to archive and make accessible, under the conditions specified below and in appropriate University policies, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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