Sleep has critical roles in health and regeneration, and one of those is clearing the brain of metabolic waste, according to researchers from the US and Denmark.
Now, as reported in the journal Nature Communications, they’ve discovered in mice that the time of day matters, suggesting the process is controlled by circadian rhythms.
“Our group has shown that just being awake or asleep drastically changes how well the brain can clear waste,” says lead author Lauren Hablitz from the University of Rochester Medical Centre.
“When you’re asleep, cerebrospinal fluid [CSF] can enter the brain and more waste is cleared. Sleep ‘cleans’ the brain.”
We are most likely to sleep when we’ve been awake for a long time or when it’s night-time and our circadian clock kicks in – anyone who has experienced jetlag knows how powerful that biological process is.
Hablitz and colleagues wanted to know if the timing of sleep impacted the brain’s cleaning process, which the group, led by senior author Maiken Nedergaard, first discovered in 2012 and elegantly named the “glymphatic system”.
The team looked at different parts of the glymphatic system across the day, including the location of a water channel (aquaporin 4, or AQP4), which has been a focus of sleep, neurodegeneration and aging research.
They found the system works better when the animal would normally be asleep – in mice this “rest phase” is during the day.
Then they explored the movements of CSF (which is vital for maintaining healthy brain function) to the lymph nodes – “a hub for the immune system”, explains Hablitz.
They discovered that CSF goes to the lymph nodes during the active phase – at night in mice – and showed that the location of AQP4 is “super important”. Losing that rhythm, says Hablitz, disrupts the brain and lymph node redistribution.
That there is a rhythm to glymphatic function wasn’t a huge surprise, she says, because most things regulated by sleep have an underlying rhythm.
The fact that CSF can redistribute to different places at different times leads to a new mechanism of communication between the brain and immune system that Hablitz says hasn’t been discussed before.
APQ4 also adds new insights, she says. “The fact that it’s necessary for brain and lymph node CSF rhythms, and that the scaffold that holds it together may be driving the rhythm, is super cool and gives us new targets beyond just this channel.”
What does this mean?
“For the general population, this suggests that it isn’t simply being asleep that matters,” says Hablitz, “but when you sleep. Think about napping – normally not as effective as regular sleep. This may be why.”
To extend their findings, the team aims to investigate impacts of things that disrupt circadian rhythms in the real world, such as altered light and sleep.
“Chronic sleep disruption and shift work are associated with neurodegeneration and increased risk of getting sick,” says Hablitz, “and these observations could be because the brain’s waste removal system and brain/immune crosstalk is not timed correctly.”