The brain’s ability to remove toxic buildup slows down with age, making aging a key risk factor for neurological disorders. Dementia, Parkinson’s, and other neurological diseases could be seen as “dirty brain” disorders in which the brain struggles to clear out harmful compounds that contribute to their development. However, research recently published in the journal Nature Aging suggests that it is possible to reverse these age-related effects and restore the brain’s waste-clearing processes.
The glymphatic system
“This research shows that restoring cervical lymph vessel function can substantially rescue the slower removal of waste from the brain associated with age,” said Douglas Kelley, PhD, a professor of Mechanical Engineering at the University of Rochester Hajim School of Engineering and Applied Sciences. “Moreover, this was accomplished with a drug already being used clinically, offering a potential treatment strategy.” Kelley is one of the lead authors of the study, along with Maiken Nedergaard, MD, DMSc, co-director of the University’s Center for Translational Neuromedicine.
The glymphatic system is the brain’s unique waste-removal process that uses cerebrospinal fluid (CSF) to wash away excess proteins generated by energy-hungry neurons and other cells in the brain during normal activity. This first description in 2012 pointed the way for potential new approaches to treating diseases commonly associated with the accumulation of protein waste in the brain, such as Alzheimer’s (beta-amyloid and tau) and Parkinson’s (alpha-synuclein). Typically, in healthy and young brains, the glymphatic system does a good job of flushing away these toxic proteins, however, as we age, this system slows, setting the stage for these diseases to develop.
Drawing waste from the brain
Once it is full of waste CSF in the skull needs to travel to the lymphatic system to the kidneys where it is processed along with other bodily waste. This research combines advanced imaging techniques with particle tracking techniques to describe in detail this route via the cervical lymph vessels in the neck, through which half of dirty CSF exits the brain.
In addition to measuring this flow, the researchers were able to record the pulsing of lymph vessels in the neck that help to draw CSF out of the brain.
“Unlike the cardiovascular system which has one big pump, the heart, fluid in the lymphatic system is instead transported by a network of tiny pumps,” said Kelley.
These microscopic lymphangions pumps have valves to prevent backflow and they are strung together, one after another, to form lymph vessels.
According to the researchers, as the mice aged, the frequency of these contractions decreased, and the valves failed; which resulted in the speed of dirty CSF flowing out of the brains of older mice being 63% slower when compared to younger animals.
Restarting the flow of brain-cleaning fluids
The researchers explored whether or not they could revive the lymphangions. In doing so they were able to identify a drug called prostaglandin F2α, which is a hormone-like compound commonly used medically to induce labor and is known to aid smooth muscle contraction.
Lymphangions are lined with smooth muscle cells, and when the researchers applied the drug to the cervical lymph vessels in older mice, the frequency of contractions and the flow of dirty CSF from the brain increased and returned to levels of efficiency found in younger mice.
“These vessels are conveniently located near the surface of the skin, we know they are important, and we now know how to accelerate function,” said Kelley. “One can see how this approach, perhaps combined with other interventions, could be the basis for future therapies for these diseases.”
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References/Sources/Materials provided by:
https://www.rochester.edu/newscenter/cleaning-up-the-aging-brain-616872/
https://www.urmc.rochester.edu
