A non-circadian role for clock-genes in sleep homeostasis: a strain comparison.
A non-circadian role for clock-genes in sleep homeostasis: a strain comparison.
复制标题
DOI：
10.1186/1471-2202-8-87
复制
发表时间：
2007-10-18
期刊：
影响因子：
2.4
通讯作者：
O'Hara BF
中科院分区：
文献类型：
--
作者：
Franken P;Thomason R;Heller HC;O'Hara BF
我们以前曾报道，睡眠剥夺(SD)后，大脑皮层中生物钟基因的表达增加，并且在缺乏一个或多个时钟基因的小鼠中，SD后的睡眠反弹会减弱。我们假设，除了产生昼夜节律外，时钟基因还在睡眠的动态平衡调节中发挥作用。在这里，我们跟踪时钟基因周期(PER)-1，PER2，和时钟控制基因白蛋白D结合蛋白(DBP)在6小时SD和随后的恢复睡眠中表达的时间进程，在三个近交系小鼠中，SD后的稳态睡眠反弹有所不同。我们推测，如果时钟基因在功能上与睡眠稳态有关，那么SD引起的基因表达变化应该根据睡眠反弹的基因类型差异而有所不同。3个品系在动物清醒时PER表达均增加，但睡眠反弹最小的品系DBA/2J(D2)在SD期间的增加速率以及6h后PER的相对增加最高。此外，尽管在其他两个品系中，随着睡眠的恢复，PER1和PER2恢复到对照水平，但在D2小鼠中，PER2的表达仍保持高水平。DBP在光照期间的表达在基线和SD期间都有所增加，尽管在后一种情况下与基线相比水平有所降低。与PER2相反，只有在D2恢复睡眠的情况下，DBP的表达才恢复到对照水平，而在其他两个品系中，DBP的表达仍然下降。这些发现支持并扩展了我们之前的发现，即前脑中的时钟基因与睡眠的动态平衡调节有关，并表明持续、高水平的PER2表达可能对恢复睡眠产生负面影响。
We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which the homeostatic sleep rebound following SD differs. We reasoned that if clock genes are functionally implicated in sleep homeostasis then the SD-induced changes in gene expression should vary according to the genotypic differences in the sleep rebound. In all three strains per expression was increased when animals were kept awake but the rate of increase during the SD as well as the relative increase in per after 6 h SD were highest in the strain for which the sleep rebound was smallest; i.e., DBA/2J (D2). Moreover, whereas in the other two strains per1 and per2 reverted to control levels with recovery sleep, per2 expression specifically, remained elevated in D2 mice. dbp expression increased during the light period both during baseline and during SD although levels were reduced during the latter condition compared to baseline. In contrast to per2, dbp expression reverted to control levels with recovery sleep in D2 only, whereas in the two other strains expression remained decreased. These findings support and extend our previous findings that clock genes in the forebrain are implicated in the homeostatic regulation of sleep and suggest that sustained, high levels of per2 expression may negatively impact recovery sleep.
登录
查看更多内容
影响因子：
56.9
作者：
Balsalobre, A;Brown, SA;Schibler, U
通讯作者：
Schibler, U
DOI：
10.1073/pnas.0602006103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Franken, P;Dudley, CA;McKnight, SL
通讯作者：
McKnight, SL
影响因子：
3.4
作者：
Masubuchi, S;Honma, S;Honma, K
通讯作者：
Honma, K
影响因子：
56.9
作者：
Dudley, CA;Erbel-Sieler, C;McKnight, SL
通讯作者：
McKnight, SL
影响因子：
4.4
作者：
Hida, A;Koike, N;Tei, H
通讯作者：
Tei, H