The autonomic and sensory nervous systems are derived from the neural crest and are required for the normal functioning of visceral organ systems, including the bladder and urethra (lower urinary tract, LUT). Surprisingly little is known about the molecular factors involved in the normal development and maturation of LUT innervation. Serotonin receptor 5-HT3A (encoded by gene Htr3a) was found to be significantly enriched in differentiating autonomic neurons innervating the LUT. A variety of pharmacological, physiological, and behavioral approaches were used to determine the roles of 5-HT3A in the development of LUT innervation. Over-stimulating 5-HT3A in sacral neural crest cells in vitro disrupted neuronal differentiation outcomes and inhibited neurite outgrowth in pelvic ganglia explants. Loss of 5-HT3A in vivo resulted in a transient disturbance of PG autonomic neuronal subtypes and an increase in autonomic and sensory neuronal fibers innervating the bladder. Male Htr3a knockout mice exhibited increased urinary voiding frequency and decreased bladder voiding efficiency. Overall, the work presented in this dissertation highlights a previously unknown role for 5-HT3A signaling in peripheral nervous system development and its requirement for normal adult urinary tract function.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-01102018-102319 |
| Date | 11 January 2018 |
| Creators | Ritter, Karen Elaine |
| Contributors | E. Michelle Southard-Smith, Rebecca A. Ihrie, Randy D. Blakely, Roger R. Dmochowski |
| 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-01102018-102319/ |
| Rights | restrictone, 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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