As aging organisms decrease, the brain loses the ability to cleanse the waste, a scenario that scientists believe could contribute to neurodegenerative situations such as Alzheimer’s disease and Parkinson’s disease, among others. Now, researchers at the University of Washington Medical School in St. Louis Report have found a way around this problem, aiming for the network of ships that drain the waste from the brain. The rejuvenation of these ships have shown, improves memory in old mice.
The study, published online on March 21st in Cell magazine, lays the groundwork for the development of cognitive decline treatments related to the age that goes beyond the challenges facing conventional drugs struggling to pass through the blood -brain barrier to reach the brain.
The natural blood-brain barrier prevents the effectiveness of neurological disorders. With the aim of a network of ships outside the brain that is critical to brain health, we see cognitive improvements in mice, opening a window to develop more powerful treatments for preventing or delaying cognitive decline. “
Jonathan Kipnis, PhD, Alan A. and Edith L. Wolff distinguished Professor of Pathology & Immunology and BJC researcher at Washu Medicine
Waste removal improves memory
Kipnis is a specialist in the field of blossom of neurosology, the study of how the immune system affects the brain in health and diseases. A decade ago, the Kipnis laboratory discovered a network of ships surrounding the brain – known as meningeal lymph nodes – in mice and people who drain the liquid and waste in the lymph nodes, where many immune cells inhabit and monitor signs of infection. He and his colleagues have also shown that some Alzheimer’s research therapies are more effective in mice when combined with a treatment that improves the drainage of fluid and debris by the brain.
Starting at the age of 50, people begin to experience a decrease in brain fluid flow as part of normal aging. For the new study, Kipnis collaborated with Marco Colonna, MD, Robert Rock Belliveau, MD, Professor of Pathology and asked if the enhancement of the operation of an old drainage system can improve memory.
To test the memory of the mice, the researchers put two identical black bars in the cage for twenty minutes to explore old mice. The next day, mice again received one of the black bars and a new object, a silver rectangular prism. Mice remembering to play with the black rod will spend more time with the new object. But old mice spend a similar time playing with the two objects.
The first author of the new study, Kyungdeok Kim, PhD, a postdoctoral collaborator at the Kipnis Laboratory, strengthened the operation of lymphatic vessels in old mice with treatment that stimulates the development of vessels, allowing more waste to drain the brain. He found that older mice with refreshed lymphatic vessels spent more time with the new object – improved memory index – compared to older mice that did not give treatment.
“A functional lymphatic system is critical to the health and memory of the brain,” Kim said. “Therapies that support the health of the body management system can have health benefits for a natural aging brain.”
The shocking brain cleaning crew
When the lymphatic system is so weakened that the waste accumulates in the brain, the weight of the cleansing falls into the immunocytic cells of the brain, called microgly. But this local cleaning crew fails to keep up with chaos and is exhausted, Kipnis explained.
The new study found that overwhelmed cells produce a danger signal, an immune protein called interleukin 6, or IL-6, which acts on brain cells to promote cognitive reduction in mice with damaged lymph vessels. Looking at the brains of such mice, the researchers found that neurons had an imbalance in the types of signals they received from the surrounding brain cells. Specifically, the neurons received fewer signals that work such as noise cancellation headphones between the cacophony of neuronal communications. This imbalance, caused by elevated IL-6 levels in the brain, has led to changes in the way the brain is wired and affected proper brain function.
In addition to improving memory in elderly mice, the treatment with lymphatic reinforcement of the vessel also caused the fall of IL-6 levels, restoring the brain noise cancellation system. The findings show the ability to improve the health of the brain’s lymphatic vasures to maintain or restore cognitive abilities.
“As we mark the 10th anniversary of the discovery of the brain’s lymphatic system, these new findings provide information on the importance of this system for brain health,” Kipnis said. “Targeting the most easily accessible lymphatic vessels outside the brain can prove to be an exciting new border in the treatment of brain disorders. We may not be able to rejuvenate the neurons, but we may be able to ensure optimal function.”
Kim K, Abramishvili D, du S, Papadopoulos Z, Cao J, Herz J, Smirnov I, Thomas JL, Colonna M, Kipnis J. Meningeal Lymphatics-Microglia Axis regulates synaptic physiology. Cell. March 21, 2025.
This project was supported by the National Institute of Aging of the National Institutes of Health (NIH), AG034113 and AG078106 grant numbers. The BJC researcher program at the University of Washington in St. Louis. The Innovation of Innovation of Neuroscience. and the Korean National Research Foundation, a grant number 2021r1a6a3A14045044. The content is the sole responsibility of the authors and does not necessarily represent NIH’s official views.
Jonathan Kipnis is co -founder of Rho Bio and holds patents and temporary applications related to the work presented here.
Source:
Magazine report:
Kim, K., et al. (2025). The axis of meningeal lymphatic-micropylia regulates synaptic physiology. Cell. doi.org/10.1016/j.cell.2025.02.022.
