Terao A, Greco M A, Davis R W, Heller H C, Kilduff T S
Molecular Neurobiology Laboratory, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
Neuroscience. 2003;120(4):1115-24. doi: 10.1016/s0306-4522(03)00395-6.
Previous studies have documented changes in expression of the immediate early gene (IEG) c-fos and Fos protein in the brain between sleep and wakefulness. Such expression differences implicate changes in transcriptional regulation across behavioral states and suggest that other transcription factors may also be affected. In the current study, we examined the expression of seven fos/jun family member mRNAs (c-fos, fosB, fos related antigen (fra)1, fra-2, junB, c-jun, and junD) and three other IEG mRNAs (egr-1, egr-3, and nur77) in mouse brain following short-term (6 h) sleep deprivation (SD) and 4 h recovery sleep (RS) after SD. Gene expression was quantified in seven brain regions by real-time reverse transcription-polymerase chain reaction (RT-PCR). Multivariate analysis of variance revealed statistically significant variation in cerebral cortex, basal forebrain, thalamus and cerebellum. Levels of c-fos and fosB mRNA were elevated during SD in all four of these brain regions. In the cerebral cortex, junB mRNA was also elevated during SD whereas, in the basal forebrain, fra-1 and fra-2 mRNA levels increased in this condition. During RS, the only IEG mRNA to undergo significant increase was fra-2 in the cortex. C-jun and junD mRNAs were invariant across experimental conditions. These results indicate that the expression of fos/jun family members is diverse during SD. Among other IEGs, nur77 mRNA expression across conditions was similar to c-fos and fosB, egr-1 mRNA was elevated during SD in the cortex and basal forebrain, and egr-3 mRNA was elevated in the cortex during both SD and RS. The similarity of fosB and nur77 expression to c-fos expression indicates that these genes might also be useful markers of functional activity. Along with our previous results, the increased levels of fra-2 and egr-3 mRNAs during RS reported here suggest that increased mRNA expression during sleep is rare and may be anatomically restricted.
以往的研究已经记录了大脑中即早基因（IEG）c-fos和Fos蛋白在睡眠和觉醒状态之间的表达变化。这种表达差异暗示了不同行为状态下转录调控的变化，并表明其他转录因子也可能受到影响。在本研究中，我们检测了短期（6小时）睡眠剥夺（SD）以及SD后4小时恢复睡眠（RS）后小鼠大脑中7种fos/jun家族成员mRNA（c-fos、fosB、fos相关抗原（fra）1、fra-2、junB、c-jun和junD）以及其他3种IEG mRNA（egr-1、egr-3和nur77）的表达。通过实时逆转录聚合酶链反应（RT-PCR）对7个脑区的基因表达进行定量分析。多变量方差分析显示，大脑皮层、基底前脑、丘脑和小脑存在统计学上的显著差异。在这四个脑区中，c-fos和fosB mRNA的水平在SD期间均升高。在大脑皮层，junB mRNA在SD期间也升高，而在基底前脑，fra-1和fra-2 mRNA水平在这种情况下增加。在RS期间，唯一显著增加的IEG mRNA是大脑皮层中的fra-2。c-jun和junD mRNA在不同实验条件下保持不变。这些结果表明，fos/jun家族成员的表达在SD期间是多样的。在其他IEG中，nur77 mRNA在不同条件下的表达与c-fos和fosB相似，egr-1 mRNA在大脑皮层和基底前脑的SD期间升高，egr-3 mRNA在SD和RS期间大脑皮层均升高。fosB和nur77与c-fos表达的相似性表明，这些基因也可能是功能活动的有用标志物。结合我们之前的结果，此处报道的RS期间fra-2和egr-3 mRNA水平的升高表明，睡眠期间mRNA表达增加的情况很少见，且可能在解剖学上受到限制。
