Asai M, Yoshinobu Y, Kaneko S, Mori A, Nikaido T, Moriya T, Akiyama M, Shibata S
Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, 2-5879-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan.
J Neurosci Res. 2001 Dec 15;66(6):1133-9. doi: 10.1002/jnr.10010.
Aging alters circadian components such as the free-running period, the day-to-night activity ratio and photic entrainment in behavioral rhythms, and 2-deoxyglucose uptakes and neuronal firing in the suprachiasmatic nucleus (SCN). A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which Period (Per) and Cryptochrome (Cry) genes play a role in negative feedback. The circadian rhythm systems include photic entrainment, clock oscillation, and outputs of clock information such as melatonin production. In this experiment, we examined clock gene expression to determine whether circadian input, oscillation, and output are disrupted with aging. Circadian expression profiles of rPer1, rPer2, or rCry1 mRNA were very similar in the SCN, the paraventricular nucleus of the hypothalamus (PVN), and the pineal body of young and aged (22-26 months) rats. On the other hand, the photic stimulation-induced rapid expression of Per1 and Per2 in the SCN was reduced with aging. The present results suggest that the molecular mechanism of clock oscillation in the SCN, PVN, and pineal body is preserved against aging, whereas the impairment of Per1 induction in the SCN after light stimulation may result in impaired behavioral photic entrainment in aged rats.
衰老会改变昼夜节律的组成部分，如自由运转周期、昼夜活动比率以及行为节律中的光诱导同步，还会改变视交叉上核（SCN）中的2-脱氧葡萄糖摄取和神经元放电。小鼠SCN中的核心生物钟机制似乎涉及一个转录反馈环，其中周期基因（Per）和隐花色素基因（Cry）在负反馈中发挥作用。昼夜节律系统包括光诱导同步、生物钟振荡以及诸如褪黑素分泌等生物钟信息的输出。在本实验中，我们检测了生物钟基因的表达，以确定昼夜节律的输入、振荡和输出是否会随着衰老而被破坏。年轻和老年（22 - 26个月）大鼠的SCN、下丘脑室旁核（PVN）以及松果体中rPer1、rPer2或rCry1 mRNA的昼夜表达谱非常相似。另一方面，随着衰老，SCN中光刺激诱导的Per1和Per2的快速表达会降低。目前的结果表明，SCN、PVN和松果体中生物钟振荡的分子机制在衰老过程中得以保留，而光刺激后SCN中Per1诱导的受损可能导致老年大鼠行为光诱导同步受损。
