Alvarez-López C, Cernuda-Cernuda R, García-Fernández J M
Department of Morphology and Cell Biology, Oviedo University, 33071 Oviedo, Spain.
Brain Res. 2006 May 4;1087(1):134-41. doi: 10.1016/j.brainres.2006.03.022. Epub 2006 Apr 13.
Endogenous rhythms of mammals are controlled by the clock located in the suprachiasmatic nucleus (SCN). The molecular mechanism of a clock involves transcription/translation-based feedback loops in which the expression of the so called "clock genes" is suppressed periodically by their protein products. Previous studies reported influence of the eye itself on the circadian oscillation of the SCN, apart from the well-known photic readjustment of the central clock. With this in mind, we decided to analyze the mPer1 clock gene expression in the retinally degenerate (rd) mouse SCN by means of immunohistochemical techniques. Our objective was to detect possible alterations of the daily endogenous oscillation of PER1 protein in the SCN of these rd mice, as well as to make clear whether or not this protein was involved in the resetting of the central clock in a manner similar to wild-type animals. We found that the endogenous levels of PER1 protein were reduced in the SCN of rd mice throughout the 24-h cycle, which suggests that loss of classic photoreceptors influences somehow the main mechanism of the SCN clock. Light stimulation induced a parallel increase of Per1 expression at the subjective night, but not at the subjective day, in both rd and wild-type mice. Therefore, SCN readjustment by light in the rd mice occurs with a pattern similar to wild-type controls, despite the reduced PER1 protein levels detected. The effect of retinal degeneration on the circadian system and the possible interactions between the retinal and the SCN clocks are discussed.
哺乳动物的内源性节律由位于视交叉上核（SCN）的生物钟控制。生物钟的分子机制涉及基于转录/翻译的反馈回路，在这个回路中，所谓“生物钟基因”的表达会被它们的蛋白质产物周期性地抑制。先前的研究报道，除了众所周知的中枢生物钟的光调节作用外，眼睛本身对SCN的昼夜节律振荡也有影响。考虑到这一点，我们决定通过免疫组织化学技术分析视网膜退化（rd）小鼠SCN中mPer1生物钟基因的表达。我们的目的是检测这些rd小鼠SCN中PER1蛋白每日内源性振荡的可能变化，以及弄清楚这种蛋白是否像野生型动物一样参与中枢生物钟的重置。我们发现，在整个24小时周期中，rd小鼠SCN中PER1蛋白的内源性水平都降低了，这表明经典光感受器的丧失以某种方式影响了SCN生物钟的主要机制。在主观夜间，光刺激在rd小鼠和野生型小鼠中均诱导Per1表达平行增加，但在主观白天则不然。因此，尽管检测到rd小鼠中PER1蛋白水平降低，但光对rd小鼠SCN的重新调节与野生型对照的模式相似。本文讨论了视网膜退化对昼夜节律系统的影响以及视网膜与SCN生物钟之间可能的相互作用。
