Paternostro M A, Meisami E
Department of Physiology and Biophysics, University of Illinois, Urbana 61801.
Brain Res Dev Brain Res. 1994 Dec 16;83(2):151-62. doi: 10.1016/0165-3806(94)00811-6.
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.
我们最近报告称，出生后甲状腺功能减退会导致大鼠嗅上皮（OE）表面积和细胞数量显著减少，从这种状态恢复时会伴随着这些参数的代偿性生长和恢复。为了探究嗅觉神经发生的相关变化，即基底细胞（BCs）的有丝分裂活性以及发育中的嗅觉受体神经元（ORNs）的迁移和存活情况，在出生后第10天、第25天和第75天的甲状腺功能减退大鼠中注射[3H]胸腺嘧啶核苷，并通过定量放射自显影检查OE，以确定注射后第1天、第5天和第15天BC和ORN区域标记细胞核的密度。将这些数据与年龄匹配的对照组以及在哺乳期结束时（出生后第25天）从甲状腺功能减退中恢复的年轻成年大鼠的数据进行比较。通过在饮用水中从出生开始给予丙硫氧嘧啶（PTU）（1 g/l）10天、25天和90天来诱导甲状腺功能减退；在出生后第25天停止给予PTU来诱导恢复。结果表明，在哺乳期甲状腺功能减退的大鼠中，BC和ORN区域标记细胞核的密度没有显著改变。在出生后第75天的甲状腺功能减退大鼠中，注射后1天标记的BC细胞核密度未受影响，但注射后5天显著高于对照组（36%）；出生后第75天注射大鼠的ORN区域神经元细胞核密度在注射后5天和15天显著降低（分别降低56%和37%）。数据表明，甲状腺功能减退的幼鼠中BC的有丝分裂活性及其向ORN区域的迁移不受影响，但出生后即甲状腺功能减退的断奶后生长大鼠中发育中的ORN的迁移和/或存活显著减少。在出生后第25天从甲状腺功能减退中恢复并在出生后第75天注射标记胸腺嘧啶核苷的大鼠中，与正常大鼠相比，标记的BC细胞核密度显著增加（注射后第1天和第5天分别增加48%和43%），表明神经发生水平升高；然而，ORN细胞核密度与对照组相同。结果表明甲状腺激素对大鼠嗅觉受体层中的嗅觉神经发生具有关键的调节作用，尤其是在断奶后时期。
