Overexpression of Prokineticin 2 in Transgenic Mice Leads to Reduced Circadian Behavioral Rhythmicity and Altered Molecular Rhythms in the Suprachiasmatic Clock.
Overexpression of Prokineticin 2 in Transgenic Mice Leads to Reduced Circadian Behavioral Rhythmicity and Altered Molecular Rhythms in the Suprachiasmatic Clock.
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DOI：
10.5334/jcr.170
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发表时间：
2018-11-06
影响因子：
--
通讯作者：
Zhou QY
中科院分区：
文献类型：
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作者：
Li X;Zhang C;Zhou QY
在哺乳动物中，驱动昼夜节律的主起搏器被认为位于下丘脑前部的视交叉上核（SCN）中。 SCN 神经元内的分子时钟机制已被阐明。相比之下，人们对 SCN 昼夜节律起搏器发送计时信息以最终控制生理和行为节律的输出机制知之甚少。两种分泌分子，前动力蛋白 2 (PK2) 和加压素，由各自的时钟控制基因编码，已被指定为候选 SCN 输出分子。已经出现的几条证据支持 PK2 作为 SCN 生物钟输出信号的作用，包括缺乏 PK2 或其受体 PKR2 的小鼠的昼夜节律降低。在目前的研究中，已经产生了过度表达PK2的转基因小鼠。这些转基因小鼠表现出 SCN 中 PK2 表达的振荡减少和昼夜运动节律幅度降低，支持 PK2 在昼夜节律调节中的重要信号作用。在转基因小鼠的 SCN 中也观察到了分子节律的改变，这表明 PK2 信号也调节核心发条装置的运行。这一结论与最近的报告一致，最近的报告显示 PK2 可能从本质上感光的视网膜神经节细胞到 SCN 神经元的信号传导作用。因此，PK2 信号在 SCN 生物钟的输入和输出通路中都发挥作用。
In mammals, the master pacemaker driving circadian rhythms is thought to reside in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. A clear view of molecular clock mechanisms within the SCN neurons has been elucidated. In contrast, much less is known about the output mechanism by which the SCN circadian pacemaker sends timing information for eventual control of physiological and behavioral rhythms. Two secreted molecules, prokineticin 2 (PK2) and vasopressin, that are encoded by respective clock-controlled genes, have been indicated as candidate SCN output molecules. Several lines of evidence have emerged that support the role of PK2 as an output signal for the SCN circadian clock, including the reduced circadian rhythms in mice that are deficient in PK2 or its receptor, PKR2. In the current study, transgenic mice with the overexpression of PK2 have been generated. These transgenic mice displayed reduced oscillation of the PK2 expression in the SCN and decreased amplitude of circadian locomotor rhythm, supporting the important signaling role of PK2 in the regulation of circadian rhythms. Altered molecular rhythms were also observed in the SCN in the transgenic mice, indicating that PK2 signaling also regulates the operation of core clockwork. This conclusion is consistent with recent reports showing the likely signaling role of PK2 from the intrinsically photosensitive retinal ganglion cells to SCN neurons. Thus, PK2 signaling plays roles in both the input and the output pathways of the SCN circadian clock.