Luo Peng-Hao, Shu Yu-Mian, Ni Rong-Jun, Liu Ya-Jing, Zhou Jiang-Ning
CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, China.
CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, China; School of Architecture and Civil Engineering, Chengdu University, Chengdu, China.
Neuroscience. 2020 Jun 15;437:145-160. doi: 10.1016/j.neuroscience.2020.04.027. Epub 2020 Apr 25.
The day-active tree shrew may serve as an animal model of human-like diurnal rhythms. However, the molecular basis for circadian rhythms in this species has remained unclear. In the present study, we investigated the expression patterns of core circadian genes involved in transcriptional/translational feedback loops (TTFLs) in both central and peripheral tissues of the tree shrew. The expression of 12 core circadian genes exhibited similar rhythmic patterns in the olfactory bulb, prefrontal cortex, hippocampus, and cerebellum, while the hypothalamus exhibited the weakest oscillations. The rhythms in peripheral tissues, especially the liver, were much more robust than those in brain tissues. ARNTL and NPAS2 were weakly rhythmic in brain tissues but exhibited almost the strongest rhythmicity in peripheral tissues. CLOCK and CRY2 exhibited the weakest rhythms in both central and peripheral tissues, while NR1D1 and CIART exhibited robust rhythms in both tissues. Most of these circadian genes were highly expressed at light/dark transitions in both brain and peripheral tissues, such as ARNTL and NPAS2 peaking at dusk while PERs peaking at dawn. Additionally, the peripheral clock was phase-advanced relative to the brain clock, as there was a significant advance (2-4 h) for PER3, DBP, NR1D1 and NR1D2. Furthermore, these genes exhibited an anti-phasic relationship between the diurnal tree shrew and the nocturnal mouse (i.e., 12-h phasing differential). Collectively, our findings demonstrate a characteristic expression pattern of core circadian genes in the tree shrew, which may provide a means for elucidating molecular mechanisms of diurnal rhythms.
日行性树鼩可能是类人昼夜节律的动物模型。然而，该物种昼夜节律的分子基础仍不清楚。在本研究中，我们调查了树鼩中枢和外周组织中参与转录/翻译反馈环（TTFLs）的核心昼夜节律基因的表达模式。12个核心昼夜节律基因在嗅球、前额叶皮层、海马体和小脑中表现出相似的节律模式，而下丘脑的振荡最弱。外周组织，尤其是肝脏中的节律比脑组织中的节律更强健。ARNTL和NPAS2在脑组织中的节律较弱，但在外周组织中表现出几乎最强的节律性。CLOCK和CRY2在中枢和外周组织中的节律最弱，而NR1D1和CIART在两种组织中均表现出强健的节律。这些昼夜节律基因中的大多数在脑和外周组织的光/暗转换时高表达，例如ARNTL和NPAS2在黄昏时达到峰值，而PERs在黎明时达到峰值。此外，外周生物钟相对于脑生物钟相位提前，因为PER3、DBP、NR1D1和NR1D2有显著提前（2-4小时）。此外，这些基因在日行性树鼩和夜行性小鼠之间表现出反相位关系（即12小时的相位差异）。总的来说，我们的研究结果证明了树鼩中核心昼夜节律基因的特征性表达模式，这可能为阐明昼夜节律的分子机制提供一种方法。
