Axotomy results in major changes in BDNF expression by dorsal root ganglion cells: BDNF expression in large trkB and trkC cells, in pericellular baskets, and in projections to deep dorsal horn and dorsal column nuclei

Brain derived neurotrophic factor (BDNF) is normally expressed by a small n umber of predominantly trkA-expressing dorsal root ganglion cells. Using im munocytochemistry and in situ hybridization, we have examined the effect of sciatic nerve section on the expression of BDNF in the adult rat. Followin g axotomy there was a long lasting (4-week) increase in BDNF mRNA and prote in in large-diameter, trkB- and trkC-expressing dorsal root ganglion cells. By 2 days postaxotomy, expression of BDNF mRNA had increased from 2% of tr kB cells to 50%, and from 18% of trkC cells to 56%. In contrast, BDNF expre ssion in most trkA cells was unchanged, although was increased in the small population of medium- and large-sized trkA cells. Following axotomy, BDNF- immunoreactive terminals appeared in the central axonal projections of larg e-diameter cells, including the deep dorsal horn and gracile nucleus. Neuro peptide Y was also upregulated following axotomy and was coexpressed with B DNF in the cell bodies and central terminals of the large cells. Ultrastruc tural analysis in lamina IV of the spinal cord revealed that BDNF terminals in these central projections establish synaptic contacts. Immunoreactivity at 4 weeks was also observed in pericellular baskets that contained calcit onin gene-related peptide (CGRP) and surrounded trkA- and trkB-expressing c ells in L4 and L5 lumbar ganglia. These baskets are likely to arise from lo cal, highly immunoreactive, BDNF/CGRP/trkA-expressing cells. Our results id entify several novel targets for BDNF and imply that it acts locally in bot h autocrine and paracrine modes, as well as centrally in a synaptic mode, t o modulate the response of somatosensory pathways in nerve injury.