Molecular biological analyses of age-related olfactory dysfunction

我们使用不同的小鼠模型和免疫组织化学方法研究了与年龄相关的嗅黏膜退行性变的病理生理学基础。甲咪唑诱导的神经上皮变性的分析表明，尽管16月龄的小鼠嗅觉神经上皮仍具有重建神经上皮和支配嗅球的能力，但16月龄小鼠的最终解剖恢复不如年轻小鼠。对重建神经上皮的细胞动力学分析表明，这种重建神经上皮能力的年龄相关性下降与神经上皮损伤后其增殖活性的增龄性降低有关，而不是与神经元分化过程中的变化有关。我们还制备了卵巢切除小鼠和雌激素受体β基因敲除小鼠，以检测雌激素对嗅黏膜动态平衡的影响。

We investigated the pathophysiology underlying age-related progression in degeneration of the olfactory mucosa using various mouse models and immunohistochemical methods. The analyses of mechimazole-induced neuroepithelial degeneration revealed that although mouse olfactory neuroepithelium retained the capacity to reconstitute neuroepithelium as well as innervate the olfactory bulb even in 16-month-old mice, the final anatomical recovery was less complete in 16-month-old mice compared with the younger mice. Cell kinetics analyses of the reconstituting neuroepithelium suggested that such a age-related decline in the capacity to reconstitute neuroepithelium is associated with its age-related decrease in proliferative activity after the neuroepithelial injury rather than changes in the process of neuronal differentiation.We also prepared ovariectomized mice and bled estrogen receptor beta-knockout mice to examine the involvement of estrogen in the homeostasis of olfactory mucosa.