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As sleep often becomes lighter and disrupted as we get older, the study potentially reinforces and explains the links between aging, sleep deprivation and the 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, co-director of the Center for Translational Neuromedicine Center. 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 slow and steady brain and cardiopulmonary activity associated with non-REM deep sleep is optimal for the functioning of the glymphatic system, the brain's unique process for eliminating waste. The findings could also explain why some forms of anesthesia can lead to cognitive impairment in the elderly.
Wash the garbage
Nedergaard and his colleagues first described the previously unknown glymphatic system in 2012. Previously, scientists did not 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.
As 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 weakening of the glymphatic system due to a sleep disturbance could be a factor of the disease. This corresponds to clinical observations showing an association between sleep deprivation and the increased risk of Alzheimer's disease.
In this study, the researchers conducted experiments on anesthetized mice with six different treatment 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.
"The synchronized waves of neuronal activity during deep slow sleep, and more precisely the trigger patterns that move from the front to the back of the brain, coincide with what we know of the CSF flow in the gathhatic system, "says Lauren Hablitz, associate postdoctoral fellow in Nedergaard's lab 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. The researchers realized that as we get older, it becomes more and more difficult to systematically achieve non-REM deep sleep, and this study reinforces the importance of deep sleep for the smooth functioning of the glymphatic system.
The study also demonstrates that improved sleep can manipulate the glymphatic system, which could indicate potential clinical approaches, such as sleep therapy or other methods to improve sleep quality, at risk populations.
In addition, since many of the compounds used in the study were analogous to anesthetics used clinically, the study also highlights the cognitive difficulties often encountered by older patients after surgery and suggests classes of drugs that can help prevent this phenomenon. The mice in the study that researchers exposed to anesthetics that did not cause slow brain activity saw their glymphatic activity decreased.
"Cognitive impairment after anesthesia and surgery is a major problem," says coauthor Tuomas Lilius of the Center for Translational Neuromedicine at the University of Copenhagen in Denmark. "A significant percentage of elderly patients undergoing surgery experience a postoperative period of delirium or new or worse cognitive impairment upon discharge."
Additional researchers from the University of Rochester and the University of Copenhagen contributed to the study. The National Institute of Neurological Disorders and Stroke, the National Institute of Aging, the Adelson Foundation, the Sigrid Juselius Foundation, the Novo Nordisk Foundation and the Lundbeck Foundation have lent their support to the research .
Source: University of Rochester