Present address: Cameco MS/Neuroscience Research Center, Saskatoon City Hospital, Room 5800, 701 Queen Street, Saskatoon, Saskatchewan, Canada, S7K 0M7.
Neurotrophin-3 down-regulates trkA mRNA, NGF high-affinity binding sites, and associated phenotype in adult DRG neurons
Article first published online: 22 SEP 2003
European Journal of Neuroscience
Volume 18, Issue 6, pages 1535–1548, September 2003
How to Cite
Gratto, K. A. and Verge, V. M. K. (2003), Neurotrophin-3 down-regulates trkA mRNA, NGF high-affinity binding sites, and associated phenotype in adult DRG neurons. European Journal of Neuroscience, 18: 1535–1548. doi: 10.1046/j.1460-9568.2003.02881.x
- Issue published online: 22 SEP 2003
- Article first published online: 22 SEP 2003
- Received 3 March 2003, revised 23 June 2003, accepted 2 July 2003
- sensory neuron;
- substance P;
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.