Illustration: Nadia Alzoubi and Natalie Hauglund
The brain’s clean-up operation during sleep is triggered by noradrenaline, mouse research reveals.
The driving force behind the brain’s waste disposal system is noradrenaline. Brief pulses of noradrenaline activate a kind of blood vessel pump during deep sleep. This causes cerebrospinal fluid to move through the brain, carrying away waste – including toxic proteins. A predominantly Danish team of neurobiologists uncovered this mechanism through research in mice (Cell, 8 January). The sleeping drug zolpidem disrupts the noradrenaline waves in mice, and with them the removal of waste.
Back in 2021, fellow researchers had already discovered that noradrenaline levels in the brain fluctuate during non-REM sleep (Current Biology). The neurotransmitter peaks every 50 seconds. Only now has it become clear what the consequence of this is: the noradrenaline waves set waste removal in motion. The Danish researchers made this discovery thanks to a new method in which they measure sleep and wake stages alongside fluctuations in blood volume and cerebrospinal fluid in freely moving mice wearing a small measuring device on their heads. For much sleep research, scientists use mice under anaesthesia so that the head can be fixed in place and measurements taken easily. According to the researchers behind the current study, this approach misses a great deal of information about genuine sleep – information they are now able to retrieve.
The noradrenaline waves turn out to coincide with fluctuations in blood volume and cerebrospinal fluid. When the Danish team stimulate noradrenaline release directly, they observe blood vessels in the brain contracting. This produces a kind of pumping motion, which then drives cerebrospinal fluid through the brain, flushing out protein waste. This clean-up action is one of the most important functions of sleep.
That makes it all the more concerning that the newly discovered mechanism is disrupted by sleep medication. When researchers administer the widely used sleeping drug zolpidem to mice, the noradrenaline waves weaken and the amount of noradrenaline decreases by 50 per cent. These mice fall asleep more quickly, but the movement of cerebrospinal fluid through the brain – and with it the processing of waste – is considerably less effective. ‘More and more people are using sleep medication, and it is very important to know whether it provides healthy sleep’, says first author Natalie Hauglund in a press release. ‘If people are not getting all the benefits of sleep, they need to be aware of that, so they can make informed decisions.’ According to the researchers, the current study may offer leads for better sleep medication: ‘Now that we know noradrenaline is the driving force behind waste clearance in the brain, we can start figuring out how to give people good, restorative sleep’, says senior author Maiken Nedergaard.
‘More and more people are using sleep medication, and it is very important to know whether it provides healthy sleep’