Han Bing, Kikuta Shu, Kamogashira Teru, Kondo Kenji, Yamasoba Tatsuya
Department of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Front Neurosci. 2022 Dec 1;16:1029279. doi: 10.3389/fnins.2022.1029279. eCollection 2022.
The circadian system, which is essential for the alignment of sleep/wake cycles, modulates adult neurogenesis. The olfactory epithelium (OE) has the ability to generate new neurons throughout life. Loss of olfactory sensory neurons (OSNs) as a result of injury to the OE triggers the generation of new OSNs, which are incorporated into olfactory circuits to restore olfactory sensory perception. This regenerative potential means that it is likely that the OE is substantially affected by sleep deprivation (SD), although how this may occur remains unclear. The aim of this study is to address how SD affects the process of OSN regeneration following OE injury. Mice were subjected to SD for 2 weeks, which induced changes in circadian activity. This condition resulted in decreased activity during the night-time and increased activity during the daytime, and induced no histological changes in the OE. However, when subjected to SD during the regeneration process after OE injury, a significant decrease in the number of mature OSNs in the dorsomedial area of the OE, which is the only area containing neurons expressing NQO1 (quinone dehydrogenase 1), was observed compared to the NQO1-negative OE. Furthermore, a significant decrease in proliferating basal cells was observed in the NQO1-positive OE compared to the NQO1-negative OE, but no increase in apoptotic OSNs was observed. These results indicate that SD accompanied by disturbed circadian activity could induce structurally negative effects on OSN regeneration, preferentially in the dorsomedial area of the OE, and that this area-specific regeneration delay might involve the biological activity of NQO1.
昼夜节律系统对睡眠/觉醒周期的调节至关重要，它还能调节成体神经发生。嗅觉上皮（OE）终生都有产生新神经元的能力。OE损伤导致嗅觉感觉神经元（OSN）丧失，会触发新OSN的产生，这些新产生的OSN会融入嗅觉回路以恢复嗅觉感知。这种再生潜力意味着OE很可能会受到睡眠剥夺（SD）的显著影响，尽管其发生方式尚不清楚。本研究的目的是探讨SD如何影响OE损伤后OSN的再生过程。将小鼠进行2周的SD处理，这会引起昼夜活动的变化。这种情况导致夜间活动减少，白天活动增加，且未在OE中诱导组织学变化。然而，在OE损伤后的再生过程中进行SD处理时，与NQO1阴性的OE相比，观察到OE背内侧区域成熟OSN的数量显著减少，该区域是唯一含有表达NQO1（醌脱氢酶1）的神经元的区域。此外，与NQO1阴性的OE相比，在NQO1阳性的OE中观察到增殖的基底细胞显著减少，但未观察到凋亡的OSN增加。这些结果表明，伴有昼夜节律紊乱的SD可能会对OSN再生产生结构性负面影响，优先影响OE的背内侧区域，并且这种区域特异性的再生延迟可能与NQO1的生物学活性有关。
