Li Xuewen, Tong Meimei, Wang Li, Qin Yumei, Yu Hongmeng, Yu Yiqun
School of Life Sciences, Shanghai University, Shanghai, China.
Ear, Nose and Throat Department, Yuecheng People's Hospital, Shaoxing, China.
Front Aging Neurosci. 2020 Dec 17;12:602688. doi: 10.3389/fnagi.2020.602688. eCollection 2020.
Aging is an important factor affecting function of smell, leading to the degeneration of mature olfactory sensory neurons and inducing the occurrence of smell loss. The mammalian olfactory epithelium (OE) can regenerate when subjected to chemical assaults. However, this capacity is not limitless. Inactivation of globose basal cells and failure to generate sensory neurons are the main obstacles to prevent the OE regeneration. Here, we found the significant attenuation in mature sensory neuronal generation and apparent transcriptional alternation in the OE from aged mice compared with young ones. The recruitment of leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)-positive cells in injured OE was weakened in aged mice, and more Lgr5+ cells remained quiescence in aged OE postinjury. Lineage-traced progenies from Lgr5+ cells were significantly fewer in the OE with aging. Moreover, Notch activation enhanced the neuronal regeneration in aged OE, making the regenerative capacity of aged OE comparable with that of young animals after injury. The growth and morphology of three-dimensional (3D)-cultured organoids from the OE of young and aged mice varied and was modulated by small molecules regulating the Notch signaling pathway. Thus, we concluded that activation of Lgr5+ cells in injured OE was age dependent and Notch activation could enhance the capacity of neuronal generation from Lgr5+ cells in aged OE after injury.
衰老作为影响嗅觉功能的一个重要因素，会导致成熟嗅觉感觉神经元的退化并引发嗅觉丧失。哺乳动物的嗅觉上皮（OE）在遭受化学攻击时能够再生。然而，这种能力并非无限。球状基底细胞的失活以及无法生成感觉神经元是阻碍OE再生的主要障碍。在此，我们发现与年轻小鼠相比，老年小鼠的OE中成熟感觉神经元生成显著减少，且存在明显的转录变化。老年小鼠受损OE中富含亮氨酸重复序列的G蛋白偶联受体5（Lgr5）阳性细胞的募集减弱，并且更多的Lgr5 +细胞在老年OE损伤后保持静止。随着衰老，OE中Lgr5 +细胞的谱系追踪后代显著减少。此外，Notch激活增强了老年OE中的神经元再生，使老年OE损伤后的再生能力与年轻动物相当。来自年轻和老年小鼠OE的三维（3D）培养类器官的生长和形态各不相同，并受到调节Notch信号通路的小分子的调控。因此，我们得出结论，受损OE中Lgr5 +细胞的激活具有年龄依赖性，并且Notch激活可以增强老年OE损伤后Lgr5 +细胞的神经元生成能力。
