Department of Physiology, Faculty of Biology, University of Murcia, Murcia, Spain.
J Biol Rhythms. 2013 Aug;28(4):249-61. doi: 10.1177/0748730413495521.
Clock gene expression is not only confined to the master circadian clock in the suprachiasmatic nucleus (SCN) but is also found in many other brain regions. The phase relationship between SCN and extra-SCN oscillators may contribute to known differences in chronotypes. The Octodon degus is a diurnal rodent that can shift its activity-phase preference from diurnal to nocturnal when running wheels become available. To understand better the relationship between brain clock gene activity and chronotype, we studied the day-night expression of the Period genes, Per1 and Per2, in the SCN and extra-SCN brain areas in diurnal and nocturnal degus. Since negative masking to light and entrainment to the dark phase are involved in the nocturnalism of this species, we also compare, for the first time, Per expression between entrained (EN) and masked nocturnal (MN) degus. The brains of diurnal, MN, and EN degus housed with wheels were collected during the light (ZT4) and dark (ZT16) phases. Per1 and Per2 mRNA levels were analyzed by in situ hybridization. Within the SCN, signals for Per1 and Per2 were higher at ZT4 irrespective of chronotype. However, outside of the SCN, Per1 expression in the hippocampus of EN degus was out of phase (higher values at ZT16) with SCN values. Although a similar trend was seen in MN animals, this day-night difference in Per1 expression was not significant. Interestingly, daily differences in Per1 expression were not seen in the hippocampus of diurnal degus. For other putative brain areas analyzed (cortices, striatum, arcuate, ventromedial hypothalamus), no differences in Per1 levels were found between chronotypes. Both in diurnal and nocturnal degus, Per2 levels in the hippocampus and in the cingulate and piriform cortices were in phase with their activity rhythms. Thus, diurnal degus showed higher Per2 levels at ZT4, whereas in both types of nocturnal degus, Per2 expression was reversed, peaking at ZT16. Together, the present study supports the hypothesis that the mechanisms underlying activity-phase preference in diurnal and nocturnal mammals reside downstream from the SCN, but our data also indicate that there are fundamental differences between nocturnal masked and entrained degus.
生物钟基因的表达不仅局限于视交叉上核（SCN）的主生物钟，也存在于许多其他脑区。SCN 和 SCN 外振荡器之间的相位关系可能有助于解释已知的不同时间类型。八齿鼠是一种昼行性啮齿动物，当有跑步轮时，它可以将其活动相偏好从昼行性转变为夜行性。为了更好地理解大脑时钟基因活性与时间类型之间的关系，我们研究了昼行性和夜行性八齿鼠的 SCN 和 SCN 外脑区中 Period 基因 Per1 和 Per2 的昼夜表达。由于该物种的夜行性涉及到对光的负掩蔽和对暗相的适应，我们还首次比较了适应（EN）和掩蔽的夜行性（MN）八齿鼠之间的 Per 表达。有轮辋的昼行性、MN 和 EN 八齿鼠的大脑在光照（ZT4）和黑暗（ZT16）阶段收集。通过原位杂交分析 Per1 和 Per2 的 mRNA 水平。在 SCN 内，无论时间类型如何，Per1 和 Per2 的信号在 ZT4 时更高。然而，在 SCN 之外，EN 八齿鼠海马中的 Per1 表达与 SCN 值不同步（ZT16 时值更高）。尽管在 MN 动物中也出现了类似的趋势，但这种 Per1 表达的昼夜差异并不显著。有趣的是，在昼行性八齿鼠的海马体中没有观察到 Per1 表达的每日差异。对于分析的其他假定脑区（皮质、纹状体、弓状、腹内侧下丘脑），不同时间类型之间的 Per1 水平没有差异。在昼行性和夜行性八齿鼠中，海马体以及扣带回和梨状皮质中的 Per2 水平与它们的活动节律同步。因此，昼行性八齿鼠在 ZT4 时表现出更高的 Per2 水平，而在两种类型的夜行性八齿鼠中，Per2 表达相反，在 ZT16 时达到峰值。总的来说，本研究支持这样一种假设，即昼夜哺乳动物活动相偏好的机制位于 SCN 下游，但我们的数据也表明，掩蔽和适应的夜行性八齿鼠之间存在根本差异。
