Danish scientists at the University of Copenhagen have concluded that the common prescription sleeping pill zolpidem causes disruptions in the oscillations of the neurotransmitter norepinephrine, which activates the brain's glymphatic system. This system removes toxic proteins from the organ. The study is published in the scientific journal Cell. The glymphatic system is a network in the brain responsible for excreting waste products such as amyloid and tau proteins. These are linked to Alzheimer's disease and other neurodegenerative diseases. Unlike other organs, the brain does not have traditional lymphatic vessels to remove waste. Instead, it relies on cerebrospinal fluid (CSF) to flush out toxins through specialized spaces surrounding blood vessels. Researchers conducted a series of experiments on mice to observe how the glymphatic system works during sleep. The scientists concluded that the oscillatory release of norepinephrine outside the REM phase of REM sleep acts as the primary driver of cerebrospinal fluid flow, with microexcitations serving as a secondary, parallel process. To investigate the effects of zolpidem on sleep architecture and glymphatic activity, experts administered the drug to a group of mice and monitored norepinephrine levels, blood vessel dynamics, and cerebrospinal fluid flow. Although zolpidem helped the mice fall asleep faster, it significantly disrupted the ultra-slow fluctuations in norepinephrine levels and blood vessel vasomotorics that are crucial for glymphatic clearance. As a result, the drug interfered with restorative processes in the brain during sleep. According to the scientists, the discovery will help improve brain health prevention in the treatment of insomnia.






