Astrocytes are one type of glia in the central nervous system, and they provide metabolic and structural support to neurons. Following injury astrocytes undergo an injury stress response known as reactive gliosis. Gliosis is characterized by both morphological and functional changes including increased cell migration. Astrocyte migration is seen in multiple disease states including glaucoma, age-related macular degeneration and glial scar formation. Migration relies upon multiple signaling pathways, many of which are activated by increases in calcium. One such source of calcium influx is the transient receptor potential vanilloid 1 (TRPV1) channel, which has a high calcium conductance and is expressed by astrocytes. Using a wound healing model, I found that antagonism of TRPV1 reduced both astrocyte migration and calcium influx following injury. Increases in calcium can drive cytoskeletal remodeling to facilitate migration, and I found that TRPV1 antagonism reduced alpha-tubulin intensity and induced retraction of both actin and alpha-tubulin in astrocytes following injury. My results suggest that in astrocytes TRPV1 is activated by injury, and that this activation contributes to injury-induced migration through an influx of calcium and subsequent cytoskeletal remodeling. By better understanding the events that underlie astrocyte migration, we can target astrocyte reactivity and migration to promote neuronal survival.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-10132014-160147 |
| Date | 15 October 2014 |
| Creators | Ho, Karen W |
| Contributors | David Calkins, Bruce Carter, Gregg Stanwood, Kevin Currie, Vsevolod Gurevich, Rebecca Sappington |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-10132014-160147/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto 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 Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, 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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