Brain clearance of toxins is reduced during sleep and anesthesia, challenging the idea that sleep's primary function is to clear these toxins
If proven correct, it could change the way we look at sleep's role in clearing waste from out brain.
Sleep has long been thought to play a crucial role in clearing metabolites and toxins from the brain through the "glymphatic system" - a proposed mechanism where cerebrospinal fluid flows through brain tissue to flush out waste products, especially during sleep. However, a new study challenges this widely-held belief. Researchers from Imperial College London have found that brain clearance is actually reduced, not increased, during sleep and anesthesia.
The study, published in Nature Portfolio Neuroscience, used advanced imaging techniques to measure the movement and clearance of fluorescent molecules in the brains of mice. Contrary to previous findings, the researchers observed the following:
1. The movement of molecules in the brain is independent of sleep/wake states or anesthesia.
2. Brain clearance is markedly reduced during sleep and various types of anesthesia (dexmedetomidine, ketamine-xylazine, and pentobarbital).
3. Diffusion, rather than bulk flow, appears to be the primary mechanism for molecular movement in the brain.
Figure 1. Clearance of molecules from the brain using 3 forms of anesthesia (DEX, KET-XYL, PENTO - all in red) compared to awake mice (grey) and mice who are asleep (panel G).
These findings contradict the popular "glymphatic" hypothesis, which suggests that sleep enhances brain clearance through increased bulk flow of cerebrospinal fluid. Instead, the study found no evidence of increased fluid movement during sleep or anesthesia.
The researchers used both in vivo imaging and histological analysis to confirm their results. They also found a weak negative correlation between clearance and EEG delta power, suggesting that deeper sleep is associated with even lower clearance rates.
While the study doesn't negate the importance of sleep for overall health, it does challenge the notion that toxin clearance is sleep's primary function. The authors suggest that reduced clearance during sleep and anesthesia may be related to decreased cerebrospinal fluid outflow from the brain, a finding reported in previous research. This study calls for a reevaluation of our understanding of sleep's role in brain health and opens up new avenues for research into the mechanisms of brain clearance and their relationship to various neurological disorders.
Study: https://www.nature.com/articles/s41593-024-01638-y