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

Abstract

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 neuroepithelium 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.