Scientists restore brain's trash disposal system
University of Rochester Medical Center
Aging is a key risk factor because, as we grow older, our brain's ability to remove toxic buildup slows down.
However, new research in mice demonstrates
that it's possible to reverse age-related effects and restore the brain's
waste-clearing process.
"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 in 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, which appears in the journal Nature Aging, along
with Maiken Nedergaard, MD, DMSc, co-director the University's Center for
Translational Neuromedicine.
First described by Nedergaard and her colleagues in 2012, 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 discovery pointed the way for potential new approaches to treat diseases commonly associated with the accumulation of protein waste in the brain, such Alzheimer's (beta amyloid and tau) and Parkinson's (alpha-synuclein). 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.
A
network of tiny pumps draws waste from the brain
Once
laden with protein waste, CSF in the skull needs to make its way to the
lymphatic system and ultimately the kidneys, where it is processed along with
the body's other waste. The new research combines advanced imaging and particle
tracking techniques to describe for the first time in detail the route via the
cervical lymph vessels in the neck through which half of dirty CSF exits the
brain.
In
addition to measuring the flow of CSF, the researchers were able observe and
record the pulsing of lymph vessels in the neck that helps 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 pumps, called lymphangions,
have valves to prevent backflow and are strung together, one after another, to
form lymph vessels.
The
researchers found that as the mice aged, the frequency of contractions
decreased, and the valves failed. As a result, the speed of dirty CSF flowing
out of the brains of older mice was 63 percent slower compared to younger
animals.
Known
drug restarts flow of brain cleaning fluids
The
team then set out to see if they could revive the lymphangions and identified a
drug called prostaglandin F2α, a hormone-like compound commonly used medically
to induce labor and known to aid smooth muscle contraction. The 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 both increased, returning to a level 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."
