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Deafferentation and neurotrophin‐mediated intraspinal sprouting: a central role for the p75 neurotrophin receptor
Author(s) -
Scott Angela L. M.,
Borisoff Jaimie F.,
Ramer Matt S.
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03838.x
Subject(s) - low affinity nerve growth factor receptor , nerve growth factor , tropomyosin receptor kinase a , neuroscience , neurotrophin , biology , axon , monoaminergic , microbiology and biotechnology , myelin , spinal cord , sprouting , receptor , central nervous system , serotonin , biochemistry , botany
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.