NERVE GROWTH-FACTOR TREATMENT INCREASES BRAIN-DERIVED NEUROTROPHIC FACTOR SELECTIVELY IN TRKA-EXPRESSING DORSAL-ROOT GANGLION-CELLS AND IN THEIR CENTRAL TERMINATIONS WITHIN THE SPINAL-CORD

Using immunocytochemistry and in situ hybridization, we have examined the expression of brain-derived neurotrophic factor (BDNF) and of neur otrophin receptors in dorsal root ganglion cells. In the adult rat, BD NF mRNA and protein were found mainly in the subpopulation of cells th at express the nerve growth factor (NGF) receptor trkA and the neurope ptide calcitonin gene-related peptide (CGRP). NGF increased BDNF withi n the trkA/CGRP cells to the extent that almost 90% of trkA cells cont ained BDNF mRNA after intrathecal NGF treatment, and 80-90% of BDNF-ex pressing cells contained trkA. Non-trkA cells that expressed BDNF incl uded some trkC cells and some small cells that labeled with the lectin Griffonia simplicifolia IB4, a marker for cells that do not express t rks. However, very few trkB cells expressed either BDNF mRNA or protei n, and NGF did not increase BDNF expression in non-trkA cells. BDNF pr otein was anterogradely transported both peripherally and centrally. T he central transport resulted in BDNF immunoreactivity in CGRP contain ing terminal arbors in the dorsal horn of the spinal cord, and this im munoreactivity was increased by NGF treatment. Electron microscopic an alysis revealed that the BDNF immunoreactivity was present in finely m yelinated and unmyelinated axons and in axon terminals, where it was m ost concentrated over dense-cored vesicles. Our data do not support an autocrine or paracrine role for BDNF within normal dorsal root gangli a, but indicate that BDNF may act as an anterograde trophic messenger. NGF levels in the periphery could influence dorsal horn neurons via r elease of BDNF from primary afferents.