TRKB-LIKE IMMUNOREACTIVITY IN TRIGEMINAL SENSORY NERVE-FIBERS OF THE RAT MOLAR TOOTH-PULP - DEVELOPMENT AND RESPONSE TO NERVE INJURY

The localization of TrkB, a signal transducing receptor for brain-deri ved neurotrophic factor and neurotrophin-4, was studied in the rat man dibular molar pulp during development and following nerve injury. Sect ions were incubated with rabbit polyclonal antiserum against the catal ytic part of the TrkB receptor, thus only binding to full-length TrkB receptors, and examined by immunofluorescence microscopy and EM immuno cytochemistry. At embryonic day 17, strongly TrkB-positive fibers were located in mandibular nerve trunks, in nerve fibers of deeper mesench yme in close spatial relation to sites of future tooth development and in subepithelial nerve plexa. At postnatal days 1-12 intensely TrkB-p ositive nerve fibers surrounded and eventually invaded the developing dental papillae and pulps. In the normal adult pulp TrkB-immunoreactiv e axons were seen extending through the radicular pulp into the corona l areas. Double labelling demonstrated a considerable overlap between TrkB-like immunoreactivity and low affinity neurotrophin receptor-like immunoreactivity in the pulp, although some low affinity neurotrophin receptor-positive nerve fibers lacked TrkB-like immunoreactivity. Imm unogold electron microscopy showed TrkB-like immunoreactivity in myeli nated as well as in unmyelinated axons. One week following inferior al veolar nerve injury there was a dramatic decrease in the level of TrkB -like immunoreactivity labelling in the pulp, which paralleled an incr ease in the expression of Schwann cell low affinity neurotrophin recep tor-like immunoreactivity. The first signs of regenerating TrkB-positi ve nerve fibers were found at 4 weeks post-operative, and at 9 weeks t he distribution of pulpal TrkB-like immunoreactivity had returned to n ormal. These data indicate that brain-derived neurotrophic factor and/ or neurotrophin-4 could be target-derived factors involved in sensory trigeminal tooth pulp nerve fiber development, differentiation or rege neration.