As people age, central nervous system clearance deteriorates, and this can lead to the development of neurodegenerative diseases. New research shows how to keep the washing machine operating optimally as the brain ages, which might avoid the development of disease.
When night arrives and our heads land on the pillow, something magical happens in our brains.
While we sleep, the glymphatic system – the brain’s washing machine – removes the waste products that have accumulated during the day in the cerebrospinal fluid, enabling us to function well the next day.
The glymphatic system is therefore indispensable for people, but just like a washing machine, it can also function less well over time, with the waste products not being removed optimally.
This can lead to the development of neurodegenerative diseases such as Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis and Huntington’s.
A new study shows how to ensure that the glymphatic system does not gradually get clogged and continues to rinse the cerebrospinal fluid – night after night, year after year.
“The glymphatic system that removes metabolic waste from the brain is generally less effective than similar systems in the rest of the body, so if this system does not work optimally, harmful substances accumulate in the brain, where they can contribute to neurodegeneration. This study is a proof of principle for how to keep the glymphatic system operating optimally,” explains a researcher behind the study, Maiken Nedergaard, Professor, Center for Translational Neuromedicine, University of Copenhagen, Denmark and Center for Translational Neuromedicine, University of Rochester, NY, USA.
The research has been published in Nature Aging.
Lymphatic vessels drain the brain
The glymphatic system drains solutes and cerebrospinal fluid with waste products from the brain through a drainage pathway – like a washing machine pumping out wastewater into a drain. The fluid passes through lymphatic vessels in the neck and then to blood plasma to be processed by the liver along with other waste products from the rest of the body.
Lymphatic vessels carry about half of the fluid cleared from the brain, and if they become blocked and fluid cannot flow rapidly enough, this is like blocking the drain pipe of a washing machine.
At home, this can result in clothes not becoming clean. In the brain, waste products can accumulate.
“Unfortunately, the flow velocity and contraction frequency of lymphatic vessels begin to deteriorate with age, and this affects the condition and health of the brain,” says Maiken Nedergaard.
Applying prostaglandin F2α to lymphatic vessels
The researchers investigated whether the flow velocity of lymphatic vessels can be improved. Lymphatic vessels are surrounded by smooth muscle cells, which become fewer and fewer as people age, contributing to poor clearance.
However, because prostaglandin drugs can make the smooth muscle cells contract, the researchers applied prostaglandin F2α directly to the lymphatic vessels in the necks of mice.
They simultaneously injected fluorescent spheres into the brains of the mice to monitor whether applying prostaglandin F2α to the lymphatic vessels affected the efficiency of clearance from the brain.
“Women are given prostaglandin during childbirth to make the smooth muscle cells in the uterus contract so that the baby can be born more easily. We therefore already know this drug well,” explains Maiken Nedergaard.
Prostaglandin F2α restores lymphatic vessel function
The results were as expected. Applying prostaglandin F2α to the lymphatic vessels of the mice resulted in the fluorescent spheres being cleared more rapidly from their brains.
Maiken Nedergaard calls the results a proof of principle, but she emphasises that prostaglandin cannot be applied directly to lymphatic vessels in people’s necks.
“We have shown that this can work and have thereby identified a new target for improving the clearance of waste products from the brain and hopefully created the basis for treatment that can counteract the development of neurodegeneration,” notes Nedergaard, emphasising other ways to stimulate the lymphatic vessels in the neck – for example, through massage, which will probably also help to pump the fluid through the vessels more rapidly.
A pill inducing fluid clearance from the brain?
Maiken Nedergaard hopes that further research will show how medicine might improve the flow of fluid through the glymphatic system while we sleep.
She envisions that medicine to optimise the glymphatic system might even be developed to counteract the accumulation of harmful waste products in the brain.
“We may even be able to take a pill before we go to sleep to ensure that the glymphatic system functions optimally,” concludes Maiken Nedergaard.
