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译文:基于分子学的时差综合症研究

译者:安凌渡  时间:2013-09-20

科学家们相信他们已经找到答案,为什么当我们旅行到新时区时需要花那么长的时间去适应它。

牛津大学的研究者们说,他们发现人体中有一种“分子制动器”,可以在我们飞行时阻止光线重置生物钟——从而产生时差综合症。

发表在美国科学期刊《细胞》上的实验报告,显示当把这种“分子制动器”从实验鼠体中移除后将允许它们迅速适应(时差)。

研究者们希望这个发现有助于研制新药物以治疗时差综合症和心理疾病康复。

生物钟以白天到夜晚24小时的循环模式使我们保持节律。它调节我们在夜晚进入睡眠,同时也影响着我们的饥饿感、心情和血压。

光在生物钟运行里扮演着一个重置按钮的作用,但是当我们在世界各地飞行时却需要花费时间使我们的生物钟适应转变。由此产生的疲惫感,这种可能会持续数天的症状,被称为“时差综合症”。

主导生物钟:

这个由英国威康信托基金会资助的研究团队,在试图找出人类为什么不能马上适应(时差的原因)。他们以实验鼠作为范例,和所有哺乳动物一样核心运作为生物钟机制。

他们关注大脑中“主导生物钟”的区域,它能使身体各方面都保持同一节律,称为“视交叉上核”。

它们会寻找能改变它们回应光线的能力水平的DNA片段。

他们发现有大量的基因细胞被激活,但立刻有一种叫盐诱导激酶1Salt Inducible Kinase 1,SIK1)的蛋白质包围它们并把它们再次抑制下去。它们就像一个制动器把光的影响给限制了。

实施削弱盐诱导激酶1功能的实验,应意味着实验鼠经过六个小时后就能迅速调整自己的生物钟——只相当于从英国到印度的一次飞行时间。

生物钟重置:

拉塞尔福斯特(英)教授告诉BBC的记者:“我们减少了(盐诱导激酶150%60%的水平,这已经足够形成一个非常非常大的影响。我们看到的是,实验鼠当真能促使它们的生物钟适应,只用了一天当中的六个小时(而那些没有做实验的老鼠则需要六天去适应)。

“以前我们就知道一定有什么东西在限制生物钟,只是我们完全不知道它是什么。这项实验提供了一个基于分子学的时差综合症成因,因此,接下来将会以开发新药物作为新的目标。”

他说,一些精神疾病包括精神分裂症等与人体生物钟失调有关,所以这些发现将有望打开新的研究领域。

“分子制动器”的作用可能是防止生物钟失去稳定性,或者阻止人造光或月光重置生物钟。

英国剑桥大学的人体生物钟专家阿克席乐斯·雷蒂博士,很有信心治疗以后会“做到对症下药,而且我认为很多这方面的药物已经被研制出来了”。

他告诉BBC的记者:“我们已经能了解很多关于时差综合症的原理以及它为什么发生的原因。

“这说明了你可以通过对大脑的调节来控制生物钟,这也是这项研究的关键所在。

我们已经有可以让生物钟变长或变短的药物,我们最需要的药物,是如何让人适应切换后的新时区,而他们发现的正是这一点。”

   
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原文:'Molecular basis' for jet lag found

发现者:lylillian  来源: 发布时间:2013-09-02 类型:转载
Plane landing

Scientists believe they have figured out why it takes us so long to adapt when we travel to new time zones.

Researchers at Oxford University say they have found the "molecular brakes" that prevent light resetting the body clock when we fly - causing jet lag.

Experiments, reported in the journal Cell, showed "uncoupling" these brakes in mice allowed them to rapidly adapt.

Researchers hope the discovery will help find new drugs for jet lag and mental health treatments.

The body clock keeps us in tune with the pattern of day and night. It means we sleep at night, but also affects hunger, mood and blood pressure.

Light acts like a reset button to keep the clock to time, but when we fly around the world it takes time for our body clocks to adjust. The resulting fatigue, which can last for days, is known as jet lag

Master clock

The research team, funded by The Wellcome Trust, was trying to figure out why people do not instantly adapt. They looked in mice as all mammals have the same core body clock mechanisms.

They focused on the "master clock" in a part of the brain, which keeps the rest of the body in sync, called the suprachiasmatic nuclei

They were looking for sections of DNA that changed their activity levels in response to light.

They found a huge numbers of genes were activated, but then a protein called SIK1 went round turning them all off again. It was acting as a brake by limiting the effect of light.

Experiments to reduce the function of SIK1 meant the mice could rapidly adjust their body clock when it was shifted six hours - the equivalent of a flight from the UK to India.

Reset

Prof Russell Foster told the BBC: "We reduced levels by 50-60%, which is big enough to get a very, very big effect. What we saw was the mice would actually advance their clock six hours within a day [rather than taking six days for untreated mice].

"We've know there's been a brake on the clock for some time, but we had absolutely no idea what it is, this provides a molecular basis for jet lag and as a result new targets for potentially developing new drugs."

He said some mental health disorders including schizophrenia were linked to an out-of-tune body clock, so these findings may open up new areas for research.

The brakes are likely to be in place to prevent the body clock from becoming erratic and being reset by artificial or moon light.

Dr Akhilesh Reddy, a specialist in the body clock, at the University of Cambridge, was very confident that treatments would follow as "it is a very drugable target and I would suspect there are lots of potential drugs already developed".

He told the BBC: "We have known a lot about the basis of jet lag and why it occurs.

"This shows how you can get into the brain and manipulated the clock, which is why this study is important.

"We have drugs which can make the clock shorter or longer, what we need is to shift it to a new time zone and that is what they have done."


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