2026-06-19T05:30:35Zhttps://repository.lib.bcit.ca/oai/request

oai:repository.lib.bcit.ca:node-14542025-05-07T21:54:23Znode:32oai_pmh:all_repository_items

Deafferentation and neurotrophin-mediated intraspinal sprouting: a central role for the p75 neurotrophin receptor Axonal plasticity in the adult spinal cord is governed by intrinsic neuronal growth potential and by extracellular cues. The p75 receptor (p75(NTR)) binds growth-promoting neurotrophins (NTs) as well as the common receptor for growth-inhibiting myelin-derived proteins (the Nogo receptor) and so is well situated to gauge the balance of positive and negative influences on axonal plasticity. Using transgenic mice lacking the extracellular NT-binding domain of p75(NTR) (p75-/- mice), we have examined the influence of p75(NTR) on changes in the density of primary afferent (calcitonin gene-related peptide-expressing) and descending monoaminergic (serotonin- and tyrosine hydroxylase-expressing) projections to the dorsal horn after dorsal rhizotomy, with and without concomitant application of exogenous nerve growth factor and NT-3. We found that, in intact p75-/- mice, the axon density of all populations was equal to or less than that in wild-type mice but that rhizotomy-induced intraspinal sprouting was significantly augmented. Monoaminergic axon sprouting was enhanced in both nerve growth factor- and NT-3-treated p75-/- mice compared with similarly treated wild-type mice. Primary afferent sprouting was particularly robust in NT-3-treated p75-/- mice. These in vivo results illustrate the interactions of p75(NTR) with NTs, with their respective tropomyosin-related kinase receptors and with inhibitory myelin-derived molecules. Our findings illustrate the pivotal role of p75(NTR) in spinal axonal plasticity and identify it as a potential therapeutic target for spinal cord injury.,Peer reviewed,Published. Received 14 August 2004; Revised 7 October 2004; Accepted 25 October 2004. 2005 ISSN: 1460-9568 doi: 10.1111/j.1460-9568.2004.03838.x pmc: 15654845 English Borisoff, Jaimie Scott, Angela L. M. Ramer, Matt S. Federation of European Neuroscience Societies Text © 2005 Federation of European Neuroscience Societies Dorsal root Plasticity Neurotrophin Rhizotomy Nerve regeneration Drug effects Gene expression--Regulation Receptors Spinal cord