“It is incredibly gratifying that the Olav Thon Foundation recognises the value of long term basic research. This grant allows us to work closely together to uncover fundamental questions about how the brain handles its own waste. We hope the mechanisms we identify will benefit future patients affected by dementia,” say the two professors.
Professor Rune Enger says we have learned that the sleeping brain is far from passive.
“The blood vessels are especially active. They dilate and constrict to a much greater extent than when you are awake, and help to effectively pump cerebrospinal fluid around the skull. This process is important for removing waste products from brain tissue that can contribute to the development of dementia. Understanding and harnessing this dynamic could open new opportunities to prevent dementia,” explains Enger. He is a professor at the Institute of Medical Basic Sciences at the University of Oslo.
Researchers will study sleeping mice using specialised microscopes and imaging technology
Professors Vervaeke and Enger will use naturally sleeping mice to study how vascular dynamics affect the circulation of brain fluid, and how this is regulated by brain cells.
The project is carried out in collaboration with professor Maiken Nedergaard at the University of Copenhagen, who first described the brain’s waste clearance system and named it the glymphatic system.
“The mice will fall asleep naturally. We will then use specialised microscopes and imaging technology to study the brain’s circulation and blood vessels in real time while they sleep,” says Vervaeke.
The researchers aim to enhance mechanisms that remove waste products
Alzheimer’s disease is characterised by the deposition of waste products in brain tissue. These are substances produced in the brain throughout life that do not cause problems in healthy individuals.
In people with Alzheimer’s and other forms of dementia, deposits are found in the brain and there are often also damages to the blood vessels. The researchers’ hypothesis is that the accumulation of waste products in the vessel wall impairs the brain’s clearance of waste via the glymphatic system. This in turn leads to further vascular damage in a self reinforcing “vicious circle”.
The researchers hope to find a way to strengthen the “pumping” so that there is less plaque in vessel walls and brain tissue.
“We therefore need to look more closely at the signals that regulate the brain’s blood vessels during sleep. By influencing the vessels’ ability to constrict, one can imagine improving both vascular function and the clearance of waste,” says Enger.