Reviving the Brain’s Waste Disposal System with a Labor-Inducing Drug
New research from the University of Rochester demonstrates the potential of a drug commonly used to induce labor in restoring the brain's waste disposal system, offering new hope for treating neurological disorders such as Alzheimer’s and Parkinson’s disease. These diseases are often associated with the brain’s diminished ability to clear out harmful waste, a condition that worsens with age.
Alzheimer’s and Parkinson’s are frequently described as "dirty brain" diseases, where toxic protein buildup in the brain contributes to cognitive decline. This buildup occurs because the brain’s glymphatic system, which uses cerebrospinal fluid (CSF) to flush out waste products, becomes less efficient as we age. Recent studies in mice, led by researchers at Rochester’s Hajim School of Engineering & Applied Sciences and the Medical Center, have found a way to reverse this age-related decline.
The study, published in Nature Aging, is spearheaded by Douglas Kelley, a professor of mechanical engineering, and Maiken Nedergaard, co-director of the University’s Center for Translational Neuromedicine. Their research highlights how the function of cervical lymph vessels, which play a crucial role in draining waste-laden CSF from the brain, can be significantly restored with the application of prostaglandin F2α (PGF), a drug already in clinical use.
The glymphatic system, first described by Nedergaard and her colleagues in 2012, is integral to maintaining brain health by clearing excess proteins and other waste products. In young, healthy brains, this system efficiently removes these toxins, but its efficiency declines with age, contributing to the development of neurodegenerative diseases.
Using advanced imaging and particle-tracking techniques, the researchers were able to trace the path of CSF as it exits the brain through cervical lymph vessels in the neck. They observed that in older mice, the contractions of these lymph vessels slowed down, causing a significant reduction in the flow of waste-carrying CSF—by as much as 63 percent compared to younger mice.
The breakthrough came when the team applied PGF, known for its ability to induce smooth muscle contraction, to the lymph vessels in older mice. The drug revitalized the contractions of the lymph vessels, restoring the flow of CSF to levels seen in younger animals. This restoration of function suggests a potential therapeutic strategy for improving brain health in aging populations.
“These vessels are conveniently located near the surface of the skin. We know they are important, and we now know how to accelerate function,” says Kelley. He suggests that this approach, possibly in combination with other treatments, could form the basis for future therapies aimed at combating age-related neurological disorders.
