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The role of BDNF in the injured/regenerating sensory neuron

dc.contributor.advisorVerge, Valerie M. K.en_US
dc.contributor.committeeMemberTetzlaff, Wolframen_US
dc.contributor.committeeMemberSchreyer, Daviden_US
dc.contributor.committeeMemberSaucier, Deborah M.en_US
dc.contributor.committeeMemberKrone, Patrick H.en_US
dc.contributor.committeeMemberCorcoran, Michael E.en_US
dc.creatorGeremia, Nicole Marieen_US
dc.date.accessioned2005-12-22T11:46:17Zen_US
dc.date.accessioned2013-01-04T05:12:41Z
dc.date.available2006-12-22T08:00:00Zen_US
dc.date.available2013-01-04T05:12:41Z
dc.date.created2005-12en_US
dc.date.issued2005-12-20en_US
dc.date.submittedDecember 2005en_US
dc.description.abstractPeripheral nerve injury induces a robust regenerative state in sensory neurons that includes elevated expression of injury/regeneration-associated genes. The molecular signal(s) underlying the transition to the regenerating state are largely unknown. Brain-derived neurotrophic factor (BDNF) is the sole identified neurotrophin that is upregulated in sensory neurons following peripheral nerve injury. As members of the neurotrophin family exert a profound influence on the intact phenotype of sensory neurons, I hypothesize that injury-associated alterations in BDNF expression play a similar role in the injured/regenerating response. Antagonizing endogenous BDNF with a function-blocking antibody prevented increases in injury/regeneration-associated gene expression and decreased the growth capabilities of the injured sensory neurons. However, BDNF was not important for maintaining this cell body response in injured neurons. The elevation of BDNF expression in injured sensory neurons either through intrathecal infusion or electrical stimulation was associated with increased injury/regeneration-associated gene expression in a dose dependent manner and the latter corresponded to increased sensory axonal regeneration. Though BDNF was able to induce and enhance the intrinsic cell body response of injured sensory neurons, exogenous BDNF was not sufficient to induce an injury phenotype in intact sensory neurons. Thus, additional signals are likely induced by the injury response. In conclusion, BDNF plays a critical role in inducing the regenerative state in sensory neurons following injury and strategies aimed at elevating levels of BDNF available to the injured sensory neuron during the inductive phase improve the cell body response.en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-12222005-114617en_US
dc.language.isoen_USen_US
dc.subjectcell body responseen_US
dc.subjectp75en_US
dc.subjectalternating currenten_US
dc.subjecttrkBen_US
dc.subjectaxotomyen_US
dc.subjectbiochemical markersen_US
dc.subjectdorsal root gangliaen_US
dc.titleThe role of BDNF in the injured/regenerating sensory neuronen_US
dc.type.genreThesisen_US
dc.type.materialtexten_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

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