The new study from scientists at the University of Rochester has shown that sleep has a different effect on the removal of potentially toxic waste products from our brain compared to the waking state. In the rest of the body, a system called the lymphatic system removes waste accumulated from most cell types. This system, which consists of an interconnected network of tubes and lymph nodes, allows the passage of toxins in lymph back into the blood circulation. From here, most toxins from metabolic processes are destroyed in the liver or are otherwise disposed of by the body. However, the brain lacks a lymphatic system that is separate from the vasculature. Instead, cerebrospinal fluid passes from the large stores in the brain (ventricles) where it is made and passes around the arteries which provide blood to the whole brain. Much of the waste produced in the brain mixes with this cerebrospinal fluid (CSF) and passes around the outside of veins which leave the brain allowing the waste product to pass out of the brain also. This system has been called the glymphatic system and using new techniques, has now come under intense scrutiny from neuroscientists.
What is the main finding from the new study?
The new study suggests that during sleep, a much larger volume of CSF passes around the arteries and that consequently, there is a greater movement of waste products out of the brain. The researchers saw a very dramatic decrease in the influx of CSF around the arteries and into the brain when a mouse was awoken from a sleep state. Interestingly, researchers saw something similar when mice were anesthetized and therefore, unconscious. Again, there was a much greater influx of CSF around blood vessels and into the brain when the mice were unconscious. Interestingly, in order to explain why there was more CSF in the brain during sleep, the researchers showed that there was more space available to be occupied by CSF in the sleeping state. There seemed to be as much as a 60% increase in the space between brain cells during sleep allowing, the researchers suggest, more CSF to enter the brain during that time.
What is the significance of these findings for Alzheimer’s disease?
Previous studies have shown that the accumulation of the small protein amyloid in the brain is associated with damage to neurons if its accumulation goes unchecked. Previous studies have also shown that amyloid is cleared by the glymphatic system. In other words, neurons in the brain make amyloid but, these are normally taken out of the brain along the veins and harmlessly dealt with outside of the brain. The researchers showed that amyloid is cleared much more efficiently from the brain during sleep which is consistent with their findings of increased glymphatic flow during sleep. Essentially, the same finding was found during anesthesia that amyloid was cleared more rapidly from the brain. The scientists went on to show that certain brain neurotransmitters, particularly adrenaline [or norepinephrine (NE)] was responsible for reducing the amount of space available to CSF influx. They showed that by blocking receptors for adrenaline or NE, they could mimic in waking animals the increased clearance of CSF that was observed in the sleeping state.
What are the broad implications for this research for our understanding of sleep?
The reasons why all higher organisms have a need for sleep has been much debated over the centuries. It is well known that humans or animals deprived of sleep will eventually die. Fatal familial insomnia, an inherited disease caused by mutations in the prion gene leads to delirium, hallucinations, and subsequently death. Sleep may have many functions including the requirement for integration of new information acquired during the waking state. These new findings, however, suggest a more basic need for sleep (as even advanced Alzheimer cases who acquire no new memories still require sleep). The suggestion is that sleep is linked to the ability of the brain to allow additional high levels of CSF to enter and bathe the neurons and other cells in fluid which can absorb many toxic substances including, importantly, amyloid. Future studies may look at ways to artificially manipulate the system to increase the clearance of amyloid from the brain, thus preventing its accumulation and toxic damage to neurons.
Read more about Alzheimer’s research by Michael Mullan