O'Hara B F, Watson F L, Andretic R, Wiler S W, Young K A, Bitting L, Heller H C, Kilduff T S
Center for Sleep and Circadian Neurobiology, Department of Biological Sciences, Stanford University, CA 94305, USA.
Brain Res Mol Brain Res. 1997 Aug;48(1):73-86. doi: 10.1016/s0169-328x(97)00084-3.
Expression of c-fos has been shown to vary throughout the brain over the course of the 24-h day. The magnitude of these changes appear to be similar in a light:dark (LD) cycle or in constant dark (DD). To further examine whether the diurnal and circadian changes in c-fos and other immediate-early gene (IEG) expression in brain are related to waking behaviors such as locomotor activity, we conducted three experiments using Northern analysis. First, we compared IEG expression in nocturnal vs. diurnally active species. Second, we investigated IEG expression in a hibernating species during its active and inactive phases. Third, we examined the development of IEG expression in the young post-natal rat. As a comparison to results obtained in extra-SCN brain regions, we also examined IEG and vasopressin expression in the SCN itself across the circadian cycle. Animals maintained under a 12:12-h LD cycle were sacrificed in the morning (10:00-11:00 h, ZT2-ZT3) or night (22:00-23:00 h, ZT14-ZT15) or at the corresponding circadian times (CT) when kept in DD. Rats sacrificed in the morning always showed lower c-fos expression than at night in all brain areas examined while the reverse pattern was seen in squirrels under both LD and DD conditions, suggesting a direct correlation between c-fos message and activity. The cerebellum displayed the greatest magnitude change between morning and night (often reaching 10-fold). Among other IEGs examined, the expression of NGFI-A and junB are similar to c-fos, but of lesser magnitude, whereas c-jun appears to be invariant in the rat but is increased during the active phase in squirrels. During the hibernation season, squirrels have lower levels of c-fos consistent with their low levels of activity even during their euthermic interbout periods. c-fos expression in the cerebellum and rest of brain of 1-week-old rats sacrificed at ZT3 and ZT15 showed low levels at both timepoints whereas 2- and 3-week-old animals had higher levels at night as do adults. Among other IEGs, junB and NGFI-A again were similar to c-fos while c-jun and junD were more constant. Our observations support the idea of a diurnal rhythm of IEG expression in the CNS that is related to waking behaviors. Among IEGs, c-fos exhibits the greatest daily variation in expression.
研究表明，c-fos的表达在24小时的一天中会在整个大脑中发生变化。这些变化的幅度在光暗（LD）周期或持续黑暗（DD）条件下似乎相似。为了进一步研究大脑中c-fos和其他即刻早期基因（IEG）表达的昼夜和昼夜节律变化是否与诸如运动活动等清醒行为有关，我们进行了三项使用Northern分析的实验。首先，我们比较了夜行性和昼行性活动物种中的IEG表达。其次，我们研究了一种冬眠物种在其活跃和不活跃阶段的IEG表达。第三，我们检查了新生大鼠中IEG表达的发育情况。作为对在视交叉上核（SCN）以外的脑区获得的结果的比较，我们还检查了SCN自身在昼夜周期中的IEG和血管加压素表达。处于12:12小时LD周期下的动物在早晨（10:00 - 11:00时，ZT2 - ZT3）或晚上（22:00 - 23:00时，ZT14 - ZT15）或在DD条件下处于相应的昼夜时间（CT）时被处死。在所有检查的脑区中，早晨处死的大鼠c-fos表达总是低于晚上，而在LD和DD条件下松鼠的情况则相反，这表明c-fos信息与活动之间存在直接相关性。小脑在早晨和晚上之间表现出最大的变化幅度（通常达到10倍）。在检查的其他IEG中，NGFI-A和junB的表达与c-fos相似，但幅度较小，而c-jun在大鼠中似乎不变，但在松鼠的活跃阶段会增加。在冬眠季节，松鼠的c-fos水平较低，这与其即使在非冬眠的间歇期活动水平也较低相一致。在ZT3和ZT15处死的1周龄大鼠的小脑和大脑其他部位的c-fos表达在两个时间点都较低，而2周龄和3周龄的动物在晚上的水平与成年动物一样较高。在其他IEG中，junB和NGFI-A再次与c-fos相似，而c-jun和junD则更为恒定。我们的观察结果支持中枢神经系统中IEG表达存在与清醒行为相关的昼夜节律这一观点。在IEG中，c-fos在表达上表现出最大的每日变化。
