Replication and differentiation of olfactory receptor neurons following axotomy in the adult hamster: a morphometric analysis of postnatal neurogenesis

Abstract

Regeneration of olfactory receptor neurons following unilateral olfactory nerve section was studied in Syrian golden hamsters by morphometric procedures. Characteristic structural and histochemical features of olfactory receptor neurons were compared on the sectioned and intact sides of the nasal septum at 6, 12, 18, 33, and 130 days following axotomy. The parameters measured were epithelial thickness and the numbers of nuclei, hematoxylin-staining olfactory vesicles, olfactory marker protein (OMP)-containing neuronal perikarya, and OMP-containing olfactory vesicles. The olfactory receptor neuron population was severely depleted 6 days after axotomy. In the succeeding 12-day period there was an initially rapid, then slower return of receptor neuron numbers. Though the regenerating olfactory epithelium appeared normal by gross inspection 33 days after the lesion, morphometric analysis revealed a substantial increase in the number of olfactory receptor neurons between 33 and 130 days postlesion. At our longest survival interval, all quantitative parameters had returned to 91-99% of control values. The numbers of OMP-containing perikarya and olfactory vesicles on the sectioned side were unchanged between the sixth and 12th postlesion days, thus suggesting that neural turnover was depressed for several days following surgery. Marker protein developed in newly formed receptor neurons between 6 and 12 days after the formation of the olfactory vesicle. Consequently, the ratio between OMP-containing olfactory vesicles and hematoxylin-staining vesicles (O/H) was used as an index of neural differentiation. The O/H ratio on the sectioned side was minimal 12 days following axotomy when stem-cell division was well under way but OMP antigenicity had not yet been expressed in newly formed neurons. At 33 days postlesion, O/H ratios were slightly but significantly greater than the control value, reflecting a degree of synchrony in the regenerating receptor neuron population. The average O/H ratio on the unlesioned side was 0.667. This value, together with our other observations, was used to derive an estimate of the life span of hamster olfactory receptor neurons, approximately 25-35 days.