title: Deafferentation and neurotrophin-mediated intraspinal sprouting: a central role for the p75 neurotrophin receptor.
abstract: 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.
authors.affiliation: ICORD (International Collaboration on Repair Discoveries), The University of British Columbia, 6270 University Boulevard, Vancouver, BC, Canada, V6T 1Z4.
authors.forename: Angela L M
authors.initials: AL
authors.lastname: Scott
authors.forename: Jaimie F
authors.initials: JF
authors.lastname: Borisoff
authors.forename: Matt S
authors.initials: MS
authors.lastname: Ramer
mesh_terms: D000344:Afferent Pathways / Q000293:injuries / Q000502:physiology* / Q000601:surgery; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D019051:Rhizotomy / Q000379:methods; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D015740:Calcitonin Gene-Related Peptide