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dc.contributor.advisorSchreyer, David J.S.en_US
dc.creatorBani Hammad, Rasheed Ahmeden_US
dc.date.accessioned2010-05-10T17:21:14Zen_US
dc.date.accessioned2013-01-04T04:30:34Z
dc.date.available2011-06-22T08:00:00Zen_US
dc.date.available2013-01-04T04:30:34Z
dc.date.created2010en_US
dc.date.issued2010en_US
dc.date.submitted2010en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-05102010-172114en_US
dc.description.abstractSuccessful axon regeneration appears to depend on the development of an injury response. Dorsal root ganglion neurons exemplify the necessity of this injury response in a unique way. Peripheral nerve transection leads to development of an injury response and successful regeneration whereas central root transection does neither. The injury response may involve extracellular and intracellular pathways. To investigate the extraneuronal influences, we performed nerve transection of either the central or peripheral axon branches and studied the expression of GAP-43, a key growth associated protein, and the transcription factors ATF3, c-Jun, and STAT3. Our results show that the responses to peripheral versus central nerve transection are fundamentally different. Peripheral but not central nerve transection increases GAP-43, ATF3, and c-Jun expression. STAT3, however, is upregulated as a result of central but not peripheral nerve transection. To investigate potential intracellular signalling pathways, we applied FGF-2, an extracellular mitogen, or an analog of cAMP, an intracellular second messenger to the cut end of the peripheral axon. Our results indicate that FGF-2 and cAMP act as activators of GAP-43 expression. On the other hand, FGF-2 and cAMP act to downregulate the expression of ATF3. FGF-2 upregulates c-Jun and the activated form of STAT3. Paradoxically, the regulation of GAP-43 expression by cAMP or by FGF-2 in vivo shows opposing results from the previously reported in vitro studies. Our present results suggest that the peripheral nerve injury response may be governed by at least three different signalling pathways.en_US
dc.language.isoen_USen_US
dc.subjectSTAT3en_US
dc.subjectATF3en_US
dc.subjectcAMPen_US
dc.subjectGAP-43en_US
dc.subjecttranscription factorsen_US
dc.subjectperipheral nerve injuryen_US
dc.subjecttransectionen_US
dc.subjectdorsal root ganglionen_US
dc.subjectsensory neuronsen_US
dc.subjectFGF-2en_US
dc.subjectc-Junen_US
dc.titleMechanisms controlling the cell body response to axon injury in dorsal root ganglion neuronsen_US
thesis.degree.departmentAnatomy and Cell Biologyen_US
thesis.degree.disciplineAnatomy and Cell Biologyen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US
dc.type.materialtexten_US
dc.type.genreThesisen_US


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