Scientists find sleep may not clear brain toxins as previously thought

The brain’s ability to rid itself of toxins may be reduced during sleep, surprising new UK DRI research reveals. The study, led by Prof Bill Wisden (UK DRI at Imperial) and Prof Nick Franks (Imperial College London), is published in the journal Nature Neuroscience.

Over the past decade, a dominant theory as to why we sleep has been that the brain’s ability to clear toxins improves during sleep, or under anaesthesia. Until now it’s been thought that sleep clears toxins from the brain via the glymphatic system, a mechanism that flushes waste from the brain. But this has never been conclusively confirmed. Previous studies have used indirect means of measuring the flow of fluid through the brain.

In the new study, the researchers used a fluorescent dye to study the brains of mice, seeing how quickly the dye moved from one area of the brain to another, and was cleared from the brain. This enabled them to measure the rate of clearance of the dye from the brain directly.

The study showed that the clearance of the dye was reduced by about 30% in sleeping mice, and 50% in mice that were under anaesthetic, compared with mice that were kept awake.

Study co-leader, Prof Nick Franks, Professor of Biophysics and Anaesthetics, Imperial College London, said:

“The field has been so focused on the clearance idea as one of the key reasons why we sleep, and we were of course very surprised to observe the opposite in our results.

We found that the rate of clearance of dye from the brain was significantly reduced in animals that were asleep, or under anaesthetic.

As yet, we do not know what it is about these states that slows down the removal of molecules from the brain. The next step in our research will be to try to understand why this occurs.”

The size of molecules may affect how quickly they move through the brain, and some compounds are cleared through different systems. Therefore, the extent to which the findings are generalisable is not yet confirmed.

Study co-leader Prof Bill Wisden, Interim Centre Director of the UK DRI at Imperial, said:

“There are many theories as to why we sleep, and although we have shown that clearing toxins may not be a key reason, it cannot be disputed that sleep is important.

Disrupted sleep is a common symptom experienced by people living with dementia, however we still do not know if this is a consequence or a driving factor in the disease progression. It may well be that having good sleep does help to reduce dementia risk for reasons other than clearing toxins.

The other side to our study is that we have shown that brain clearance is highly efficient during the waking state. In general, being awake, active and exercising may more efficiently clean the brain of toxins.”

Next, the researchers aim to uncover how sleep reduces the clearance of toxins from the brain in mice, and explore whether their findings are applicable to humans.

To find out more about Profs Nick Franks and Bill Wisden's research, visit Prof Wisden's UK DRI profile, or the Franks-Wisden lab website. To stay up to date on the latest research news and institute updates, sign up to receive our monthly newsletter.

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Reference: Miao A, Tianyuan L, Hsieh B et al. Brain clearance is reduced during sleep and anesthesia. Nature Neuroscience (2024).

Article published: 13 May 2024
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