Getting a good night’s sleep is a critical part of our daily biological cycle and is associated with better brain function, a stronger immune system, and a healthier heart. On the contrary, the Sleep disorders such as insomnia and sleep apnea can significantly affect health and quality of life. Lack of sleep often precedes the onset of neurodegenerative diseases and is a predictor of early dementia.
But not everything goes for sleeping well, warns research published in the magazine ‘cell‘.
The study contains a warning for people who use the commonly prescribed sleeping pill zolpidem. The drug suppresses the glymphatic system, which could set the stage for neurological disorders such as Alzheimer’s, which result from toxic buildup of proteins in the brain.
The work describes for the first time synchronized oscillations in the brain during non-REM sleep that drive the clearance of waste associated with neurodegenerative diseases. These oscillations feed the system glymphatica brain-wide network responsible for removing proteinaceous debris, including amyloid and tau, associated with neurodegenerative diseases.
“As the brain transitions from the waking state to the sleeping state, the processing of external information decreases and processes such as glymphatic elimination of waste products are activated,” says Maiken Nedergaard, co-director of the University of Rochester Translational Neuromedicine Center (USA) and lead author of the study.
The team from the universities of Rochester and Copenhagen (Denmark) used an advanced optical technique to study brain activity in mice without the need to immobilize or anesthetize them. This allowed wake and sleep patterns to be recorded in a natural and prolonged way.
The study explored whether sleeping pills replicate the natural oscillations necessary for glymphatic function. The team focused on zolpidem, a sedative commonly prescribed to treat insomnia.
in mice
While zolpidem effectively induced sleep in mice, it also suppressed norepinephrine oscillations, disrupting the glymphatic system and impeding the brain’s waste-clearing processes, a finding that raises concerns about its long-term use.
Research highlights the importance of norepinephrine in non-REM sleep. This neurotransmitter generates «micro awakenings« that cause vasomotion, that is, the rhythmic contraction of blood vessels. These oscillations drive the movement of cerebrospinal fluid (CSF) in the glymphatic system, crucial for clearing the brain during sleep.
“These findings, combined with what we know about the glymphatic system, paint the full picture of dynamics within the brain, and these slow waves, microarousals, and norepinephrine were the missing link,” he says. Natalie Hauglundfirst author of the study.
Scientists now have a new tool and potential target for improving sleep. “The research provides a mechanistic link between norepinephrine dynamics, vascular activity and glymphatic clearance, which improves the understanding of the restorative functions of sleep,” says Nedergaard. “It also draws attention to the potentially harmful effects of certain pharmacological sleep aids on brain health, highlighting the need to preserve the natural architecture of sleep for optimal brain function.”
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