Quantitative [ 3H]thymidine autoradiography of neurogenesis in the olfactory epithelium of developing normal, hypothyroid and hypothyroid-rehabilitated rats

Abstract

We recently reported that postnatal hypothyroidism results in marked reduction in surface area and cell number in the rat olfactory epithelium (OE) and recovery from this condition is accompanied by compensatory growth and restitution of these parameters. To explore the correlative changes in olfactory neurogenesis, i.e. mitotic activity of basal cells (BCs) and migration and survival of developing olfactory receptor neurons (ORNs), hypothyroid rats at postnatal (P) days of P10, P25 and P75 were injected with [ 3H]thymidine and OE was examined by quantitative autoradiography to determine the density of labeled nuclei at the BC and ORN zones at days 1, 5 and 15 post-injection. These data were compared with those of age-matched controls as well as young adult rats allowed to recover from hypothyroidism at the end of the suckling period (P25). Hypothyroidism was induced by administration of propylthiouracil (PTU) from birth in the drinking water (1 g/l) for 10, 25 and 90 days; recovery was induced by withdrawal of PTU at P25. The results indicated that the densities of labeled nuclei in the BC and ORN zones were not significantly altered in the suckling hypothyroid rats. In the P75 hypothyroid rats density of labeled BC nuclei was unaffected 1 day after injection but was significantly (36%) more than controls 5 days after injection; the density of neuronal nuclei in the ORN zone of P75 injected rats was markedly and significantly reduced (56% and 37% at 5- and 15-days post-injection). Data indicate that mitotic activity of BCs and their migration into the ORN zone is not affected in the hypothyroid infant rats but migration and/or survival of developing ORNs are markedly reduced in the postweaning growing rats made hypothyroid from birth. In rats allowed to recover from hypothyroidism at P25 and injected with labeled thymidine at P75, the density of labeled BC nuclei were significantly increased (48% and 43% at 1- and 5-days post-injection) compared to normal rats suggesting elevated levels of neurogenesis; density of ORN nuclei, however, were the same as controls. The results indicate critical regulatory influences of thyroid hormones on olfactory neurogenesis in the rat olfactory receptor sheet, in particular during the postweaning period.