All sleep is not equal when it comes to cleaning the brain

New research shows how depth of sleep can affect our brain's ability to effectively eliminate toxic waste and protein. Since sleep often becomes lighter and disrupted as we get older, the study potentially strengthens and explains the links between aging, sleep deprivation, and increased risk of Alzheimer's disease. .

"Sleep is essential to the functioning of the brain waste disposal system and this study shows that the deeper the sleep is, the better it is," said Maiken Nedergaard, MD, DMSc., Co-Director of the Center. Translational neuromedicine from the University of Rochester Medical Center (URMC) and lead author of the study. "These findings add to the increasingly obvious evidence that quality of sleep or sleep deprivation can predict the onset of Alzheimer's disease and dementia."

The study, which appears in the newspaper Progress of science, indicates that the slow and stable brain and cardiopulmonary activity associated with non-REM deep sleep is optimal for the operation of the glymphatic system, the brain's unique process to eliminate waste. The findings could also explain why some forms of anesthesia can lead to cognitive impairment in the elderly.

The glymphatic system, hitherto unknown, was first described by Nedergaard and his colleagues in 2012. Previously, scientists did not fully understand how the brain, which maintains its own closed ecosystem, eliminates waste. The study revealed a plumbing system that grafts onto blood vessels and pumps cerebrospinal fluid (CSF) through the brain tissue to flush out waste. A subsequent study showed that this system works mainly while we sleep.

Because the accumulation of toxic proteins such as beta-amyloid and tau in the brain is associated with Alzheimer's disease, the researchers hypothesized that the deterioration of the glymphatic system due to a sleep disturbance could be a factor in the disease. This corresponds to clinical observations showing an association between sleep deprivation and the increased risk of Alzheimer's disease.

In the present study, researchers conducted experiments on anesthetized mice with six different anesthesia regimens. While the animals were under anesthesia, the researchers followed the electrical activity of the brain, cardiovascular activity and the flow of CSF purification through the brain. The team observed that a combination of drugs, ketamine and xylazine (K / X), most faithfully reproduced the slow and steady electrical activity in the brain and the slow heart rate associated with non-REM deep sleep. In addition, the electrical activity in the brains of the mice to which K / X had been administered appeared to be optimal for the functioning of the glymphatic system.

"Synchronized waves of neuronal activity during deep slow sleep, especially trigger patterns that move from the front to the back of the brain, coincide with what we know about the CSF flow into the glymphatic system, "said Lauren Hablitz, Ph.D., postdoctoral associate of Nedergaard's laboratory and first author of the study. "It seems that the chemicals involved in triggering neurons, namely ions, cause an osmosis process that helps pull fluid through brain tissue."

The study raises several important clinical questions. It further strengthens the link between sleep, aging and Alzheimer's disease. It is known that as we get older, it becomes more and more difficult to systematically obtain deep non-paradoxical sleep, and the study reinforces the importance of deep sleep for the proper functioning of the glymphatic system. The study also demonstrates that the glymphatic system can be manipulated by improving sleep, which could indicate potential clinical approaches, such as sleep therapy or other methods to improve the quality of sleep, in the elderly. populations at risk.

In addition, since many of the compounds used in this study were analogous to anesthetics used clinically, the study also highlights the cognitive difficulties often experienced by older patients after surgery and suggests classes of drugs that can be used. used to prevent this phenomenon. Study mice exposed to anesthetics that did not induce slow brain activity experienced decreased glymphatic activity.

"Cognitive impairment after anesthesia and surgery is a major problem," said Tuomas Lilius, MD, Ph.D., in collaboration with the Center for Translational Neuromedicine at the University of Copenhagen, Denmark and co-author of the study. "A significant percentage of elderly patients undergoing surgery experience a postoperative period of delirium or have a new or worsened cognitive impairment upon discharge."

Provided by
University of Rochester Medical Center