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Dissertation
Microtubule-mediated nerve regeneration: knocking down the microtubule severing protein fidgetin augments nerve regeneration in vitro and in vivo
Doctor of Philosophy (Ph.D.), Drexel University
2018
DOI:
https://doi.org/10.17918/D8M081
Abstract
The purpose of this thesis was to explore the effects of fidgetin knockdown in adult dorsal root ganglia both in vitro and in vivo. Our lab has demonstrated that fidgetin knockdown in embryonic cortical neurons increased microtubule mass and axon length. It is known that microtubules are paramount for axon growth and an effect that increases their mass and axon length is attractive as a potential regenerative target. Adult dorsal root ganglia were utilized because they are the only adult neuron capable of being cultured in a dish and they are relevant to nerve regeneration both within the peripheral and central nervous system. The adult dorsal root crush rodent injury model was used as the complementary in vivo system. In the coming pages, I describe why microtubules are essential to neurons and attractive therapeutic targets. Microtubules are paramount for nerve regeneration and the discovery of novel microtubule associated proteins, small molecules that bind tubulin to affect its stability properties, and the expansion of the tubulin code all has the potential to reveal novel therapeutic targets for regeneration. The remaining chapters describe how fidgetin knockdown in adult dorsal root ganglia neurons, in vitro, increases a specific domain of microtubule mass responsible for expanding microtubules, increases the length of axons on and off the inhibitory spots, and promotes cellular growth on and across the inhibitory spots. Finally, I conclude with our promising in vivo results that fidgetin augments nerve regeneration in vivo, thus highlighting fidgetin as a novel therapeutic target to augment nerve regeneration. Furthermore, my work serves as a "plug-and-play" system for future investigations of microtubule-based therapies and combinatorial treatments such as chondroitinase, growth factors, and other viral transductions.
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Details
- Title
- Microtubule-mediated nerve regeneration
- Creators
- Andrew Javier Matamoros - DU
- Contributors
- Bradford Aldrich Jameson (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vi, 121 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 8138; 991014632395804721