The brain’s waste removal process disrupted by sleeping pills

Sleeping pills may help you doze off, but the sleep you get may not be as restorative. When mice were given zolpidem, which is commonly found in sleeping pills such as Ambien, their brains were unable to effectively remove waste products during sleep.

Sleep is important for removing waste from the brain. At night, a clear fluid called cerebrospinal fluid circulates around brain tissue and flushes out toxins through a series of thin tubes known as the glymphatic system. Think of it like a dishwasher, which turns on your brain while you sleep, says Miken Nedergaard at the University of Rochester Medical Center in New York. However, the mechanisms that push fluid through this network have not been well understood.

Nedergaard and his colleagues implanted optical fibers into the brains of seven mice. By irradiating chemicals in the brain, the fibers can track the flow of blood and cerebrospinal fluid during sleep.

They found that elevated levels of a molecule called norepinephrine cause blood vessels in the brain to constrict, reducing blood volume and allowing cerebrospinal fluid to flow into the brain. As norepinephrine levels decrease, blood vessels dilate and cerebrospinal fluid is pushed back. Thus, fluctuations in norepinephrine during non-rapid eye movement (NREM) sleep stimulate blood vessels to act like pumps in the glymphatic system, Nedergaard said.

This discovery reveals that norepinephrine plays an important role in clearing waste from the brain. Previous research has shown that when we sleep, the brain releases norepinephrine in a slow, oscillating pattern. These norepinephrine waves occur during NREM, a sleep stage important for memory, learning, and other cognitive functions.

Next, the researchers treated six mice with zolpidem, a sleeping pill commonly sold under the brand names Ambien and Zolpimist. The mice fell asleep faster than those treated with a placebo, but the flow of cerebrospinal fluid in the brain was reduced by about 30 percent on average. In other words, “their brains aren't being cleaned very well,” Nedergaard said.

Although zolpidem was tested in this experiment, almost all sleeping pills inhibit the production of norepinephrine. This suggests that they may interfere with the brain's ability to eliminate toxins.

It is too early to tell whether these results apply to humans. “Human sleep architecture is still quite different from mice, but they have the same brain circuits studied here,” he says. laura lewis at Massachusetts Institute of Technology. “Some of these basic mechanisms may apply to us as well.”

If sleeping pills interfere with the brain's ability to eliminate toxins during sleep, Nedergaard says, that means new sleeping pills must be developed. Otherwise, your sleep problems may worsen and your brain health may deteriorate in the process.