Expression of nerve growth factor, p75, and the high affinity neurotrophin receptors in the adult rat trigeminal system: evidence for multiple trophic support systems.

We hypothesize that discrete trigeminal structures have the components required for autocrine regulation as well as redundant neurotrophin support systems. We examined the expression of nerve growth factor (NGF) and the low affinity (p75) and high affinity (trkA, trkB, and trkC) neurotrophin receptors in the trigeminal system of adult rats. Four sites were examined; the trigeminal ganglion, mesencephalic nucleus, principal sensory nucleus (PSN), and trigeminal motor nucleus. NGF was expressed by more than 60% of neurons in each area studied. NGF immunolabeling may have resulted from exogenous protein incorporated from the microenvironment or from NGF synthesized by the neuron per se. To resolve this issue, in situ hybridization for NGF mRNA was performed. The mRNA was expressed by 2/3 to 7/8 of neurons in trigeminal structures. Moreover, double-labeling studies showed that virtually every ganglion cell that was NGF-immunoreactive also expressed the NGF transcript. Neurotrophin receptors (p75 and trk isoforms) were expressed by more than 60% of the neurons in each trigeminal structure. The only exception was the PSN, where the receptors were expressed by fewer than half of the neurons. Taken together, these data imply that NGF must be elaborated by neurons that co-express both p75 and trkA. Therefore, each trigeminal structure has the machinery for autocrine/paracrine regulation, as well as the capacity for retrograde and/or anterograde trophic support. Furthermore, the co-expression of the specific trk isoforms indicates that trigeminal neurons are sensitive to more than one neurotrophin.