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Neurotrophin‐3 down‐regulates trkA mRNA, NGF high‐affinity binding sites, and associated phenotype in adult DRG neurons
Author(s) -
Gratto Kelly A.,
Verge Valerie M. K.
Publication year - 2003
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 - 10.1046/j.1460-9568.2003.02881.x
Subject(s) - tropomyosin receptor kinase a , tropomyosin receptor kinase c , low affinity nerve growth factor receptor , neurotrophin 3 , neurotrophin , nerve growth factor , biology , dorsal root ganglion , trk receptor , microbiology and biotechnology , endocrinology , medicine , neuroscience , receptor , brain derived neurotrophic factor , sensory system , genetics , neurotrophic factors , growth factor , platelet derived growth factor receptor
Neurotrophin‐3 (NT‐3) binds to multiple trks, not only its initially identified receptor trkC. Recent studies in our laboratory show that NT‐3 negatively regulates nociceptive phenotype associated with the trkA subpopulation. Due to the extensive overlap in trkA and trkC expression it is uncertain whether there is a direct influence of NT‐3 on trkA in adult sensory neurons. Thus, the aim of this study was to examine whether NT‐3 might alter trkA and associated neuronal phenotype outside of the trkC subpopulation. The effect of a seven‐day intrathecal infusion of NT‐3 on intact, uninjured adult rat dorsal root ganglion neurons was investigated. Serial sections were processed for receptor radioautography or in situ hybridization to identify and colocalize neurons expressing high‐affinity nerve growth factor (NGF) binding sites, substance P (SP), trkC, or trkA mRNAs and to examine the influence of NT‐3 on these populations. NT‐3 does not appear to alter trkC expression, but evokes a notable reduction in trkA, high‐affinity NGF binding sites, and SP levels. It is unlikely that signalling by trkC greatly influences this response because the down‐regulation of SP occurs most notably in trkA neurons that lack trkC. Moreover, we have shown here that message levels of two trkA isoforms are differentially modulated by NT‐3; infusion results in greater down‐regulation of the noninsert containing isoform. These findings suggest a clinically relevant role for NT‐3 as an antagonist to NGF, but also raise the caution that not just trkC‐positive neurons are influenced following exposure to the neurotrophin.