Sleep is definitely important for learning and memory, synaptic scaling.
Those are very important functions of sleep.
I think it sounds pretty obvious to anyone that sleep is really important for the function
of our brain.
Most of the previous studies looking at sleep deprivation have focused on the nervous system.
But when animals don't sleep, when they're prevented from sleeping, they actually die.
So it didn't really make sense that sleep would be all about the brain.
If an animal dies because of sleep deprivation, there has to be
some kind of injury somewhere in the body, right, that we hoped we could find.
So our basic question was, why is sleep essential for survival; why is it essential for life?
We really wanted to look at every tissue and really understand what was the cause of death
in sleep-deprived animals.
So we found that actually the gut was the organ that was specifically vulnerable to
sleep loss.
And this was obviously very shocking to us.
I remember Alex coming to me and telling me, "look, I see the gut -- I see this thing repeatedly,"
and we would sit down and talk about it.
I think we argued a lot with my lab mates.
I was frankly a bit skeptical about it.
I was anticipating the main effects to be in the brain.
I mean, yeah, it was definitely surprising.
But it was really clear.
That's the crazy thing.
It wasn't something difficult to find.
Once we started looking, we found it pretty quickly.
What we see in the gut that we don't see in the other tissues of the animals is increased
oxidative stress.
There's an accumulation of reactive oxygen species, and these are molecules that are
extremely chemically reactive.
So they're very unstable.
And they essentially steal electrons from other cellular macromolecules and destabilize
them and cause oxidative stress.
Their gut, and only their gut, accumulates those molecules at very high levels.
So we saw this in flies and mice, and with different methods of sleep deprivation.
The second important finding was that if you prevent ROS accumulation in the gut of sleep-deprived
flies, it can actually survive without sleep.
I think I was finally completely convinced when we were able to neutralize ROS specifically
in the gut, and we showed that the animals now lived normally, that was when I became convinced.
The questions now are, of course, why the gut?
How does the gut know that the brain is sleeping?
How does this actually kill the animal?
Right. These are all questions that we're working
on now.
But I think with this work, we start to know better where to look at.
And what to look at.
And we hope that our findings may lead in the future to an intervention that may mitigate
some of the negative outcomes of insufficient sleep.
To be honest with you, did I really think we would find this?
No.
Definitely not.
And this was something that I wanted to do for years and years and years, and I was just
really reluctant to get into it, because, what are the chances that we would figure
it out.
But then, you know, with the people in my lab, they had the best attitude ever and it
was a really good situation.