大多数人坐飞机长途旅行后都会有时差反应。英国牛津大学的研究人员发现了一种阻碍人体生物钟重新调整的基因,也许不久就能研发出可帮助人们消除痛苦的时差反应的药物。
当旅途穿越3个以上时区时,人们就容易出现时差反应。长途旅行时,我们眼中特殊的感光组织能够感知到变化,同时促使体内生物钟随当地时间调整。但生物钟每调整一个小时,人体就需要适应一天,结果便会连续几天出现不适反应,比如疲劳、失眠等。
为了弄明白为何恢复期要这么长,研究人员将处于黑暗中数小时的老鼠放置在光亮处进行了研究。
研究人员在新一期《细胞》杂志上报告说,他们发现了一个帮助老鼠体内生物钟适应光照的基因组,但其中有一个基因却起着相反的作用。当把老鼠体内的这个基因“关闭”,给它们变换3个不同时区,它们几乎没有出现时差反应。
研究人员认为,这种基因犹如一个“安全闸”,具有防止人体生物钟紊乱的作用,因为系统紊乱与众多慢性疾病有关。
牛津大学的斯图尔特·皮尔逊博士说:“我们发现了一个积极阻碍人体生物钟重新调整的系统。不过,有一个提高人体生物钟稳定性的缓冲机制也在情理之中。但也正是这个缓冲机制影响了我们适应新时区的能力,引发了时差反应。”
皮尔逊博士表示,限制这种缓冲机制作用的物质已经研究了出来,消除这种现象的药物有望在10年内上市。(生物谷 Bioon.com)
生物谷推荐的英文摘要
Cell Doi:10.1016/j.cell.2013.08.004
The CRTC1-SIK1 Pathway Regulates Entrainment of the Circadian Clock
Aarti Jagannath, Rachel Butler, Sofia I.H. Godinho, Yvonne Couch, Laurence A. Brown, Sridhar R. Vasudevan, Kevin C. Flanagan, Daniel Anthony, Grant C. Churchill, Matthew J.A. Wood, Guido Steiner, Martin Ebeling, Markus Hossbach, Joseph G. Wettstein, Giles E. Duffield, Silvia Gatti, Mark W. Hankins, Russell G. Foster, Stuart N. Peirson
Retinal photoreceptors entrain the circadian system to the solar day. This photic resetting involves cAMP response element binding protein (CREB)-mediated upregulation of Per genes within individual cells of the suprachiasmatic nuclei (SCN). Our detailed understanding of this pathway is poor, and it remains unclear why entrainment to a new time zone takes several days. By analyzing the light-regulated transcriptome of the SCN, we have identified a key role for salt inducible kinase 1 (SIK1) and CREB-regulated transcription coactivator 1 (CRTC1) in clock re-setting. An entrainment stimulus causes CRTC1 to coactivate CREB, inducing the expression of Per1 and Sik1. SIK1 then inhibits further shifts of the clock by phosphorylation and deactivation of CRTC1. Knockdown of Sik1 within the SCN results in increased behavioral phase shifts and rapid re-entrainment following experimental jet lag. Thus SIK1 provides negative feedback, acting to suppress the effects of light on the clock. This pathway provides a potential target for the regulation of circadian rhythms.