The role of neurotrophin-3 in primary sensory neurons
| dc.contributor.advisor | Verge, Valerie M. K. | en_US |
| dc.contributor.committeeMember | Krone, Patrick H. | en_US |
| dc.contributor.committeeMember | Juurlink, Bernhard H. J. | en_US |
| dc.contributor.committeeMember | Devon, Richard | en_US |
| dc.creator | Gratto, Kelly Ann | en_US |
| dc.date.accessioned | 2008-10-02T11:08:25Z | en_US |
| dc.date.accessioned | 2013-01-04T05:00:34Z | |
| dc.date.available | 2009-11-05T08:00:00Z | en_US |
| dc.date.available | 2013-01-04T05:00:34Z | |
| dc.date.created | 2002 | en_US |
| dc.date.issued | 2002 | en_US |
| dc.date.submitted | 2002 | en_US |
| dc.description.abstract | Neurotrophin-3 (NT-3) is a member of the nerve growth factor family of neurotrophins. These molecules regulate aspects of sensory neuron survival, proliferation, phenotype, regeneration, and nociception. NT-3 presumably acts upon binding to its preferred receptors, trkC and p75, but much of the literature concerning its role involves embryological studies; little is known regarding its role in the adult, aside from its part in proprioception. Here, the effect of a 7 day intrathecal infusion of NT-3 on the phenotype of intact or axotomized adult rat dorsal root ganglion (DRG) neurons was examined. Serial sections were processed for in situ hybridization and computer-assisted image analysis was undertaken to characterize the NT-3 responsive subpopulation and to compare relative levels of mRNA for neurotrophin receptors, neuropeptides, cytoskeletal elements, injury- and regeneration-associated molecules, and other markers in individual neurons. 125I-NGF was utilized to determine the influence of NT-3 on high-affinity NGF binding site densities. Data show that ~ 40% of neurons coexpress trkC and p75 mRNAs; some of these cells also exhibit transcripts for trkA, NFM, Ta1 a-tubulin, a-CGRP, SP, galanin, NPY, GAP-43, cjun, and SNAP-25 - establishing the presence of potentially functionally significant micropopulations within the trkC-positive subset. Following injury, levels of many biochemical markers are altered in a positive or negative fashion. In all cases described here, if the marker colocalizes with trkC, post-trauma treatment with NT-3 allows for a return towards normal message levels, suggesting a role for NT-3 in the maintenance of normal adult phenotype in these cells. In the intact state, NT-3 effects a reduction in trkA, high-affinity NGF binding sites, and SP levels, within non-trkC neurons. The importance of these markers in nociception suggests a role for NT-3 in analgesia. But, in addition, NT3 also reduces SNAP-25 mRNA levels in otherwise normal trkC-expressing cells, which might negatively alter their functioning. Together, these data indicate that multiple subsets of mature DRG neurons are responsive to NT-3, not all of which express trkC, and not all of which respond to the neurotrophin in the same manner: these factors must be taken into account when considering therapeutic applications for NT-3. | en_US |
| dc.identifier.uri | http://hdl.handle.net/10388/etd-10022008-110825 | en_US |
| dc.language.iso | en_US | en_US |
| dc.title | The role of neurotrophin-3 in primary sensory neurons | en_US |
| dc.type.genre | Thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Anatomy and Cell Biology | en_US |
| thesis.degree.discipline | Anatomy and Cell Biology | en_US |
| thesis.degree.grantor | University of Saskatchewan | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) | en_US |