November 2013

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Brainwashed by sleep

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A string of sleepless nights can reduce a person to a total wreck. Tasks that are usually a doddle become monumentally challenging, and you face the choice of either blundering through the entire day in a zombie-like state or becoming so drugged up on caffeine that you're constantly on edge.

Taken to the extreme, sleep deprivation can lead to poor decision-making, impair the immune system, increase the likelihood of seizures, hamper the formation of memories, cause hallucinations and even lead to death [1]. Why does lack of sleep affect us so much? What happens in these lost hours which is so crucial that we cannot live without it?

Many theories exist on why we sleep, but results from a recent study published in Science have given new weight to the idea that our brains are 'cleaned' overnight so that the next day we wake up feeling refreshed [2]. Nedergaard and her group have found evidence which suggests that while we sleep, the brain is flooded with fluid to cleanse it, a bit like a dishwasher. Put simply, each night our brain gets a good wash.

Previously, this same team of researchers found a network of tiny channels that runs through the brain [3]. All cells in the body carry out processes and reactions that produce byproducts, which can be toxic if left to accumulate. In the body, this waste is cleared away by network of tubes called the lymphatic system, which is filled with fluid called lymph, but this system does not exist in the brain. Instead, the researchers found that the cerebrospinal fluid (CSF) in which the brain floats carries away potentially toxic byproducts [2]. Since this is similar to the role played by the lymphatic system, they decided to dub this the 'glymphatic' system [4].

In order to compare the brains of mice that were awake and asleep, the lead author, Lulu Xie spent a whole two years training mice so that they could be lulled to sleep on a special two-photon microscope, which can trace the movement of dyes in a living brain [4]. When recordings of brain activity showed the mouse was definitely asleep, she injected a green dye to trace the flow of CSF in the brain. Afterwards, the same mouse was gently woken by stroking its tail, its brain activity checked once again to confirm that it was awake, and a red dye injected.

By comparing the distribution of the two dyes, the researchers could see how far the CSF had seeped into the brain [2]. When awake, the CSF was largely excluded from the brain, but when asleep or anaesthetised, the gaps between the cells grew by over 60% to allow the fluid to flow deep into the brain and flush out the waste products that had accumulated whilst the mouse's brain was awake and active.

Switching states

There is of course, no simple 'off' switch by which we can turn on or shut down our system, but there could be a trigger. This could come in the form of the accumulation of waste metabolites themselves, making us feel tired and telling us we need sleep [4]. As for what controls the process of waking up again, the authors tested whether coming out of this deep brain cleanse might be driven by the neurological signalling chemical noradrenaline [5]. By adding a substance to the surface of the brain which stimulated the release of noradrenaline, they showed that it causes the surrounding cells to swell, closing the channels and restricting the flow of fluid through the brain.

Why do we need to sleep at all during this brainwashing process? Nedergaard suggests that the brain may be unable to clean itself at the same time as carrying out all the normal daytime functions, which is why you have to switch from an alert, awake state to a state of sleep. She compares this to throwing a house party - you have to wait for the guests to leave before you can start properly cleaning up the mess [6].

Where next?

Many questions still remain – as for most scientific discoveries, this is just the start. Does this happen to all animals when they sleep? Is the accumulation of waste products actually harmful to neurons and other brain cells, and if so, how damaging is it? Do problems with this system play a role in the development of conditions such as insomnia, dementia or epilepsy?

So far, we only know that this brainwashing happens in mice, so the next step will be to use MRI scans to test whether it also happens in people [6]. If so, this could help us better understand and treat diseases where sleep is disrupted and waste builds up. For example, the group found much lower levels of β-amyloid (Aβ), which accumulates in Alzheimer's disease, after sleep [2]. So while it has generally been thought that problems with sleep in Alzheimer's disease are a symptom, these results suggest it might actually be a cause.

If nothing else, this study illustrates how little we really know about what happens when we close our eyes each night. Hopefully, this new insight will allow us to figure out why we need sleep at all, what happens to our brains when we miss out on it and how we can maximise our benefit from it.

Now if you'll excuse me, I think I'll go and have a lie down.


[1] Van Dongen, H.P. et al. (2003). The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation, Sleep, 26(2):117-26.

[2] Xie et al. (2013). Sleep Drives Metabolite Clearance from the Adult Brain, Science, 342(6156):373-7.

[3] Iliff J.J. et al. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β, Sci Transl Med., 4(147):147.

[4] Underwood, E. (2013). Sleep: The Brain’s Housekeeper? Science, 342(6156):301.

[5] Herculano-Houzel, S. (2013). Sleep It Out. Science, 342(6156):316-317.

[6] Sleep 'cleans' the brain of toxins, available from:, [accessed 28 Oct 2013].

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Respond to this article

This is a really interesting read, in addition to all of the current unanswered questions, I wonder if eventually we might also understand why some people seem to require a lot less sleep than others.

Chris Morris

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