Changes in expression of the low affinity receptor for neurotrophins, p75NGFR, in the regenerating olfactory system.

We have disrupted the integrity of the rat olfactory neuroepithelium using intranasally applied TX-100, a procedure known to reversibly eliminate the sensory neuron input from the neuroeithelium to the olfactory bulb [Margolis et al. (1974) Denervation in the primary olfactory pathway of mice: biochemical and morphological effects. Brain Res. 81, 469-483]. One week after TX-100 exposure, we observed a disruption of the pseudo-stratified organization of the neuroepithelium which was accompanied by a 60% reduction in neuroepithelial width, compared to saline-treated controls. Full recovery of the neuroepithelium was not observed until 16 weeks post-lesion. During this post-lesion period, we monitored the expression of the low affinity receptor for neurotrophins, p75NGFR, in the olfactory bulb of saline- and TX-100-treated animals, using the monoclonal antibody, MAb192. In saline-treated animals, p75NGFR-immunoreactivity (p75NGFR-ir) was localized to individual glomeruli in the olfactory bulb, with little or undetectable p75NGFR-ir in the olfactory nerve layer. We have previously reported that pre-lesioned levels of p75NGFR-ir in the glomerular layer were dramatically reduced while an induction of p75NGFR-ir was observed in the olfactory nerve layer, one and two weeks after intranasal exposure to TX-100 [Turner & Perez-Polo (1992) Regulation of the low affinity receptor for nerve growth factor, p75NGFR, in the olfactory system of neonatal and adult rat. Int. J. Devl Neurosci. 10, 343-359]. In this paper, we demonstrate that this previously reported reduction in glomerular p75NGFR-ir took 16 weeks to fully recover and was, thus, coincident with the post-lesion recovery of the neuroepithelium. In the olfactory nerve layer, the return of p75NGFR-ir to pre-lesioned levels took only four weeks. No changes in neuroepithelial width and integrity or alterations in p75NGFR-ir in the olfactory bulb were observed in saline-treated animals. Thus, the TX-100-induced removal of the peripheral input to the olfactory bulb resulted in a reversible change in expression of p75NGFR-ir in the bulb. We believe that these changes are a reflection of the regenerative capacity of the olfactory system.