It is one of the most used tablets by French people who suffer from insomnia. According to the National Institute of Health and Medical Research (Inserm), 15 to 20% of them experience difficulty sleeping. Sleeping pills appear as a temporary solution that often becomes permanent. But sleep obtained is perhaps not as restorative than it seems. In a study published on January 8, 2024, researchers found that giving mice zolpidem prevented their brains from effectively eliminating waste during sleep. Which could be associated with neurodegenerative diseases.
Sleep is essential for clearing waste from the brain. It was Danish scientist Maiken Nedergaard and her team who, in 2013, discovered this brain cleansing mechanism. In his study published in the journal Scienceshe explains that at night, cerebrospinal fluid circulates around brain tissue, removing toxins through a series of thin tubes called the glymphatic system. It is a kind of dishwasher which turns on during the night.
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“The brain cleansing system is called the glymphatic system. It is important to note that it is only activated during the deep part of sleep called non-REM sleep. This is caused by a neuromodulator called norepinephrinewhich, during non-REM sleep, is released in slow cycles approximately every 50 seconds,” explains Professor Maiken Nedergaard in a press release.
To understand the effect of sleeping pills on this waste disposal, Professor Maiken Nedergaard and her team implanted optical fibers in the brains of seven mice. By illuminating chemicals in the brain, the fibers allow them to track the flow of blood and spinal fluid during sleep.
They found that when norepinephrine levels increase, blood vessels in the brain constrict, reducing blood volume and allows cerebrospinal fluid to flow into the brain. Conversely, when this rate decreases, the blood vessels dilate, pushing the cerebrospinal fluid outwards. “This dynamic change in blood volume works like a pump to transport cerebrospinal fluid along the arteries to the brain and through brain tissue. Thus, norepinephrine coordinates constriction and the synchronized dilation of the blood vessels which control the glymphatic system”, explains the scientist.
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Next, the researchers treated six mice with zolpidem, a commonly used sleeping pill. If the mice fell asleep faster than those treated with a placebo, they found that cerebrospinal fluid flow in their brain had decreased by around 30% on averagethus interrupting the elimination of waste from the brain. “Sleep is crucial because it gives the brain time to carry out homeostatic housekeeping tasks such as eliminating waste. sleeping pills block neuromodulators which control the waste elimination system and prevent the brain from properly preparing for a new day,” she explains.
It is still too early to know whether these results will be transposed to humans. “The architecture of human sleep is still quite different from that of mice, but we have the same brain circuit than the one that was studied here”, explains to the media New Scientist Laura Lewis of the Massachusetts Institute of Technology. “It’s likely that some of these fundamental mechanisms also apply to us.”
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For Dr Clifford Segil, a neurologist at Providence Saint John’s Health Center in Santa Monica, California, USA, who was not involved in the study, “it is extremely improbable what the advantages increased sleep that occurs when patients use a sleeping pill like zolpidem are outweighed by any alleged potential adverse effects of this medication decreasing REM sleep, which then, in turn, decreases brain neurotransmitter levels, which in turn decreases brain protein levels,” he points out.
“If sleeping pills do interfere with the brain’s ability to eliminate toxins during sleep, that means we need to develop new drugs for sleep”, explains the author of the study.
