A drug used to induce labor in pregnant women has been shown to reactivate tiny waste-clearing pumps in the brains of older mice, a finding that could hold promise as a new way to combat Alzheimer's and Parkinson's diseases and general cognitive decline.
When our brains are working properly, there is an excess of proteins that are created from the energy-intensive processes that take place between our neurons. These proteins need to be cleared out so that the brain can continue to function properly. When they are not removed, they can get in the way and lead to the tangles of beta amyloid and tau protein that are a hallmark of Alzheimer’s disease, or the alpha-synuclein buildup that accompanies Parkinson’s.
In 2012, Danish neuroscientist Maiken Nedergaard first described a system that uses cerebrospinal fluid (CSF) to clear waste from the brain, which he called the glymphatic system. Now, Nedergaard and his colleagues have delved deeper into the glymphatic system, focusing on lymphatic vessels called lymphangions. These are a series of small pumps in the neck that are responsible for carrying dirty CSF out of the brain and into the lymphatic system, where it reaches the kidneys for processing.
Using advanced particle tracking in mouse models, they found that contractions in these pumps decreased as the rodents aged. As a result, they found that the brains of older mice had 63% less polluted CSF than younger mice, setting the stage for the rodents to experience cognitive decline.
Curious about whether they could get the pumps back on track, Nedergaard focused on the fact that lymphangions are lined with smooth muscle cells. So they looked at a drug called prostaglandin F2α, which works on these types of cells and is commonly used to induce labor in pregnant women. Sure enough, applying the drug to older mice in a topical cream got the pumps working again, and the team saw that the flow of dirty CSF out of the brain returned to the same level of efficiency seen in young mice.
If the findings hold up in human trials, they could offer a brand new way to combat the effects of cognitive impairment and brain-related diseases.
“These vessels are located near the surface of the skin, we know they are important, and we now know how to speed up their function,” says study co-author Douglas Kelley of the University of Rochester’s Hajim School of Engineering and Applied Sciences. “We could see this approach, perhaps combined with other interventions, become the basis for future treatments for these diseases.”
The research was published in the journal Nature Aging.
Source: University of Rochester Medical Center via EurekAlert