小鼠为何“一夜白头” | Nature Podcast

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相关文章：压力如何让小鼠体毛变灰 |《自然》论文

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Interviewer: Benjamin Thompson

First up on the show this week, we’ve got a story about a paper which looks at something that’s becoming quite close to my heart – why hair goes grey. But before we get into it, let’s look at how hair is coloured in the first place. So, within every hair follicle is a pool of cells called melanocyte stem cells, which differentiate into the pigment-producing cells that add colour to growing hair strands. But these melanocyte stem cells eventually start to dry up as humans get older, so they’re not available to top up the pigment-producing cells and hair starts to grey. But age isn’t the only reason for greying hair – stress has long been believed to play a role in it too. Here’s Ya-Chieh Hsu from Harvard University in the US.

Interviewee: Ya-Chieh Hsu

I think with regards to stress, there is definitely lots of speculation about the potential connection between stress and hair greying. I guess, however, before our work, there was no firm scientific evidence at least linking the two.

Interviewer: Benjamin Thompson

So, yes, plenty of anecdotal evidence – look at a picture of a world leader entering office and then look at one of them when they step down, for example – but now, Ya-Chieh and her colleagues report direct evidence of how stress can cause hair greying in mice, at least. In the first instance, Ya-Chieh and her colleagues wanted to show that stress was indeed capable of inducing hair greying, and they did so by subjecting groups of mice with black coats to different types of physical or psychological stresses, and these mice did indeed show signs of greying a lot faster than they normally would. The strongest effect was seen when mice were injected with a compound known as RTX – an analogue of the active ingredient in chilli peppers. To find out what was going on, Ya-Chieh looked at the hair follicles of these mice and saw that stress was having a big effect on their melanocyte stem cells.

Interviewee: Ya-Chieh Hsu

The stem cells are lost actually, in some severe cases, within five days, so that’s actually really short, which was actually a huge surprise to us.

Interviewer: Benjamin Thompson

Without the stem cells, there was no way to replenish the pigment-producing cells, and so the mice started to grey. But knowing that it happens wasn’t enough. Ya-Chieh wanted to work out exactly how stress triggers the loss of these stem cells. There have been theories that the immune system plays a role in stress-related hair greying, but Ya-Chieh showed that immunocompromised mice still went grey when injected with RTX, so their search for a culprit continued.

Interviewee: Ya-Chieh Hsu

We then thought that maybe cortisol, a stress hormone, may be involved, but that turned out to be wrong again.

Interviewer: Benjamin Thompson

In humans, cortisol levels are often raised in response to stress. However, mice that were unable to make cortisol-like hormones still went grey after being injected with RTX. So, Ya-Chieh went back to the drawing board again.

Interviewee: Ya-Chieh Hsu

So, essentially, after a lot of negative results, we finally found that stress triggers hair greying through the sympathetic nervous system.

Interviewer: Benjamin Thompson

The sympathetic nervous system is responsible for a stress response known as the ‘fight-or-flight’ response. Have you ever felt your heart start racing when you hear a sudden, loud bang? That’s your sympathetic nervous system kicking in. And it’s not just wired up to the heart.

Interviewee: Ya-Chieh Hsu

The sympathetic nerve innervates essentially all organs including the skin, and in the skin, the nerve fibres innervate each hair follicle. So, the nerve fibres are actually in close contact with the stem cells that are important in regenerating pigment.

Interviewer: Benjamin Thompson

During the fight-or-flight response, the sympathetic nervous system releases a neurotransmitter from the ends of nerve fibres. That neurotransmitter is noradrenaline, also known as norepinephrine, and it turns out that noradrenaline has quite an effect on melanocyte stem cells.

Interviewee: Ya-Chieh Hsu

What happens is that the stem cells first become hyperproliferative, which means they divide like crazy, then they start to differentiate to become these pigment-producing cells. So, once they differentiate, they start to migrate out from the hair follicle to other regions of the skin. Many hair follicles have lost all of the melanocyte stem cells so that the pigment cannot be made anymore and the hair loses its colour.

Interviewer: Benjamin Thompson

And this process was not reversible. Once the stem cells were gone, no pigment could be made. However, Ya-Chieh and her colleagues showed that suppressing the stress-induced proliferation of the stem cells prevented hair greying. And they also showed that blocking the release of noradrenaline or chemically disabling the sympathetic nervous system meant that stress had no effect on the mice’s hair colour. Christopher Deppmann, from University of Virginia in the US, researches nervous system development and has written a News and Views article about the new work. He was impressed with the thoroughness of the research.

Interviewee: Christopher Deppmann

So, this is really remarkable. It’s been almost anecdotal that stress can cause premature greying, but nobody has really understood the mechanism by which that happens. The Hsu Lab did this really beautiful series of experiments kind of basically saying, okay, well, here are all the different things that happen during stress – there’s an endocrine reaction, there’s a neuronal reaction, there’s an immune reaction – and we’re just going to one by one take them out. And by doing that molecular disp essentially, they found that it’s really the neuronal component or the ‘fight-or-flight’ component that causes the depletion of these stem cells.

Interviewer: Benjamin Thompson

Of course, this work was done in mice, and humans may react differently. Ya-Chieh does have some evidence to show that noradrenaline does have an effect on human melanocyte stem cells in vitro, but she emphasised that it’s early work. Christopher says that this research throws up other things to look at too.

Interviewee: Christopher Deppmann

I think maybe the most obvious question is whether or not this mechanism of stress-induced greying is the same as age-related greying. It would be interesting, in the future, to age mice and just kind of modulate what’s going on with their sympathetic nervous system to see if you can slow down greying or speed it up. I think that there are maybe some more esoteric questions, like is there an evolutionary component to this, and then I think that there are therapeutic implications like, could this be used to have anti-greying therapies?

Interviewer: Benjamin Thompson

Any therapies would be a long way off as this new work is just the start of the story. It does appear to answer how stress can cause hair greying, but why does the system exist at all?

Interviewee: Ya-Chieh Hsu

The real answer is I don’t know. I think we do have speculation of why this might be important and my lab is working hard to think about if we can essentially test whether there are specific reasons why this is happening in the first place. Maybe what’s important is that the sympathetic nerve provides a way to modulate the behaviour of melanocyte stem cells so that the stem cells potentially can react very quickly to other things, for example, light, for example, UV – something that you do want to produce pigment very quickly.

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来源：Nature自然科研