“The study further strengthens our understanding of how deep sleep maintains brain health,” says Tuomas Lilius, MD, PhD (University of Helsinki and University of Copenhagen), one of the authors of the study.
The study, published in Science Advances, demonstrated in a mouse model that the waste removal system of the brain functions most efficiently in conjunction with slow-wave electrical activity of the brain that occurs during deep sleep.
As with other organs, the brain accumulates waste as a result of metabolism, which must be removed. In other parts of the body, this waste management is carried out by lymphatic circulation, but the brain has a cleaning system of its own, something described by researchers as recently as 2012 (Iliff, Nedergaard & al, Sci Transl Med).
This system, known as the glymphatic system, mainly functions during sleep (Xie L et al. Science 2013) and makes cerebrospinal fluid flow through the brain tissue, thus flushing out waste, such as proteins. The recently published study demonstrated that to function efficiently, the system requires deep sleep.
Alzheimer’s disease is associated with the accumulation of amyloid beta and tau proteins in the brain, indicating problems in the functioning of the glymphatic system. It may be possible that getting too little deep sleep deters glymphatic clearance and causes neurological diseases. This assumption is supported by clinical observations that sleep disorders are associated with a heightened risk of developing Alzheimer’s disease.
Brain cleaning may also occur under anaesthesia
Dr Lilius points out that the recently published study is also of interest in terms of anaesthesiology, as the study revealed that the choice of anaesthetic may have an impact on glymphatic waste clearance.
“The results may offer a partial explanation as to why surgery or a period of intensive care has the potential to provoke cognitive disturbances in elderly patients. Such problems could perhaps be alleviated by careful choice of anaesthetic regimens that improve glymphatic flow for these patients.”
Six different drug combinations were used to anaesthetise mice in the study. The researchers found that drug combinations containing dexmedetomidine, which reduces the noradrenergic signalling of the brain, achieved a state of deep, slow-wave sleep closely resembling natural sleep.
“Dexmedetomidine improved glymphatic clearance and is already in clinical use. It has in fact been developed in Finland,” Lilius points out.
When anaesthetics that do not generate slow-wave activity in the brain were used instead, glymphatic clearance was markedly poorer.
“This study supports earlier results, according to which there is a strong link between sleep, ageing and the onset of Alzheimer’s disease. Furthermore, the findings indicated that the functioning of the brain’s glymphatic system can be manipulated by influencing quality of sleep, which may open up new clinical treatment opportunities,” notes Professor Maiken Nedergaard from the University of Rochester, who was the principal investigator of the study.
Tuomas Lilius, MD, PhD, University of Helsinki and University of Copenhagen
Reference: Lauren M. Hablitz, Hanna S. Vinitsky, Qian Sun, Frederik Filip Stæger, Björn Sigurdsson, Kristian N. Mortensen, Tuomas O. Lilius, Maiken Nedergaard. Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. Science Advances, 27 Feb 2019