“When we used the fiber flow photometry method to examine the mouse brain, we observed these slow waves of norepinephrine, but we also saw how it works in synchronization with fluctuation in blood volume,” says Hauglund.
Each time the level of norepinephrine increased, it caused the blood vessels in the brain to contract and blood volume to decrease. At the same time, the contraction increased the volume of the perivascular spaces around the blood vessels, which were immediately filled with cerebrospinal fluid.
When the level of norepinephrine dropped, the process went in reverse: the blood vessels dilated, letting blood in and pushing out cerebrospinal fluid. “What we found was that norepinephrine worked a bit like an orchestra conductor and made the blood and spinal fluid move synchronously in these slow waves,” says Hauglund.
And because the study was designed to monitor this process in freely moving, undisturbed mice, the team learned exactly when all this was happening. When the mice were awake, norepinephrine levels were much higher but relatively stable. The team observed the opposite during the REM sleep phase, where norepinephrine levels were consistently low. Oscillatory behavior was present exclusively during the NREM sleep phase.
So the team wanted to check how glymphatic clearance would work by giving the mice zolpidem, a sleeping pill that has been shown to increase NREM sleep time. In theory, zolpidem should have stimulated brain cleansing. But he turned it off instead.
Sleeping pills
“When we observed the mice after giving them zolpidem, we found that they all fell asleep very quickly. It was planned: we take zolpidem because it makes us sleep easier,” says Hauglund. “But then we saw these slow fluctuations in norepinephrine, blood volume and cerebrospinal fluid almost completely stop.”
