Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Merowinger Platz 1a, 40225 Düsseldorf, Germany.
Zoology Department, Faculty of Science, Suez University, Suez 43111, Egypt.
Int J Mol Sci. 2020 Feb 19;21(4):1394. doi: 10.3390/ijms21041394.
The circadian system is an endogenous timekeeping system that synchronizes physiology and behavior with the 24 h solar day. Mice with total deletion of the core circadian clock gene Bmal1 show circadian arrhythmicity, cognitive deficits, and accelerated age-dependent decline in adult neurogenesis as a consequence of increased oxidative stress. However, it is not yet known if the impaired adult neurogenesis is due to circadian disruption or to loss of the Bmal1 gene function. Therefore, we investigated oxidative stress and adult neurogenesis of the two principle neurogenic niches, the hippocampal subgranular zone and the subventricular zone in mice with a forebrain specific deletion of (), which show regular circadian rhythmicity. Moreover, we analyzed the morphology of the olfactory bulb, as well as olfactory function in mice. In mice, oxidative stress was increased in subregions of the hippocampus and the olfactory bulb but not in the neurogenic niches. Consistently, adult neurogenesis was not affected in mice. Although Reelin expression in the olfactory bulb was higher in mice as compared to wildtype mice (, the olfactory function was not affected. Taken together, the targeted deletion of in mouse forebrain neurons is associated with a regional increase in oxidative stress and increased Reelin expression in the olfactory bulb but does not affect adult neurogenesis or olfactory function.
生物钟系统是一种内源性的计时系统,它使生理和行为与 24 小时的太阳日同步。核心生物钟基因 Bmal1 完全缺失的小鼠表现出昼夜节律紊乱、认知缺陷,并由于氧化应激增加而加速成年神经发生的年龄依赖性下降。然而,目前尚不清楚受损的成年神经发生是由于昼夜节律紊乱还是 Bmal1 基因功能丧失所致。因此,我们研究了具有大脑特异性缺失的 ()小鼠两个主要神经发生龛位(海马颗粒下区和侧脑室下区)的氧化应激和成年神经发生,()小鼠表现出规律的昼夜节律性。此外,我们还分析了嗅球的形态以及()小鼠的嗅觉功能。在()小鼠中,海马和嗅球的部分区域的氧化应激增加,但神经发生龛位没有增加。一致地,()小鼠的成年神经发生没有受到影响。尽管与野生型小鼠相比,()小鼠嗅球中的 Reelin 表达更高(),但嗅觉功能不受影响。总之,在小鼠前脑神经元中靶向缺失()与嗅球中氧化应激的区域性增加和 Reelin 表达增加有关,但不影响成年神经发生或嗅觉功能。