Coogan Andrew N, Piggins Hugh D
3.614 Stopford Building, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Eur J Neurosci. 2005 Jul;22(1):158-68. doi: 10.1111/j.1460-9568.2005.04193.x.
It is well-established that light pulses regulate components of the extracellular signal-regulated kinases I/II (ERK) cascade in the suprachiasmatic nuclei (SCN) circadian clock. These events are important for photic-resetting of the circadian clock. The SCN circadian clock is also reset by pulses of dark, but it is unknown if this stimulus alters the activity of ERK, the transcription factor Elk-1 or expression of the immediate early gene c-fos in the SCN. Using Syrian hamsters free-running in constant light, we determined the effects of dark pulses on these factors in the SCN. In constant light, levels of phosphorylated ERK (P-ERK) showed significant circadian variation in the Syrian hamster SCN, while levels of c-Fos or phosphorylated Elk-1 (P-Elk-1) did not. A 6-h dark pulse beginning at circadian time (CT) 8 down-regulated expression of P-ERK and c-Fos, but not P-Elk-1, in the SCN. Following termination of the pulse, levels of c-Fos increased above time-matched control values, while P-ERK expression did not. When given at the beginning of the subjective night (CT13), a 6-h dark pulse did not phase-shift behavioural rhythms and failed to alter the expression of c-Fos, P-ERK, or P-Elk-1 in the SCN. At the level of the visual thalamus, expression of c-Fos in the intergeniculate leaflet was higher during the subjective night as compared to the subjective day, although dark pulses had no robust effects on expression of c-Fos or P-ELK-1 in this structure. We conclude that dark-pulse resetting of the circadian clock is complex and involves both non-photic and photic components.
众所周知,光脉冲可调节视交叉上核(SCN)生物钟中细胞外信号调节激酶I/II(ERK)级联反应的组成部分。这些事件对于生物钟的光重置很重要。SCN生物钟也可被暗脉冲重置,但尚不清楚这种刺激是否会改变ERK的活性、转录因子Elk-1或SCN中即刻早期基因c-fos的表达。我们利用在持续光照下自由活动的叙利亚仓鼠,确定了暗脉冲对SCN中这些因子的影响。在持续光照下,叙利亚仓鼠SCN中磷酸化ERK(P-ERK)水平呈现出显著的昼夜节律变化,而c-Fos或磷酸化Elk-1(P-Elk-1)水平则没有。在昼夜时间(CT)8开始的6小时暗脉冲下调了SCN中P-ERK和c-Fos的表达,但没有下调P-Elk-1的表达。脉冲结束后,c-Fos水平高于时间匹配的对照值,而P-ERK表达则没有。当在主观夜间开始时(CT13)给予6小时暗脉冲,它不会使行为节律发生相移,也不会改变SCN中c-Fos、P-ERK或P-Elk-1的表达。在视觉丘脑水平,与主观白天相比,在主观夜间,膝间小叶中c-Fos的表达更高,尽管暗脉冲对该结构中c-Fos或P-ELK-1的表达没有显著影响。我们得出结论,生物钟的暗脉冲重置是复杂的,涉及非光和光成分。