The garbage collection system of the aging brain is crucial

The brain’s ability to get out the garbage by itself may be more important than before. New research suggests that revitalizing the brain’s clearance system can improve memory in mice, potentially providing new ways to address age-related cognitive decline and neurodegenerative diseases in humans.

Scientists at the University of Washington School of Medicine have identified a way to improve the effectiveness of ships that drain waste from the brain. The study, published March 21 in the journal Journal, showed that enhancing this drainage system leads to measurable improvements in memory function in aging mice.

Dr. Jonathan Kipnis, Alan A. and Edith L. “By targeting the goal of the external brain to ship networks that are critical to brain health, we see cognitive improvements in mice, opening a window to develop more powerful therapies to prevent or delay cognitive decline.”

This method takes advantage of a relatively new discovery. Just a decade ago, Kipni’s lab identified the blood vessel network around the brain (called meningeal lymph) in both mice and humans. These blood vessels waste fluid and waste in lymph nodes, where immune cells monitor signs of infection or disease.

From around the age of 50, this drainage system begins to flow, which is part of normal aging, and has the potential to cause proteins and waste products to be associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

In the morning at the University of Washington research facility, a team of scientists worked carefully with mouse models that could eventually be translated into human treatment. Dr. Kyungdeok Kim, a postdoctoral researcher in Kipnis’ lab, has been working on understanding how the brain’s waste management system affects cognitive function.

To test the mice’s memory, Kim’s team placed two identical black rods in the cage for twenty minutes so that older mice could explore them. The next day, they reintroduced one of the familiar black poles with a new object – a silver rectangular prism. Mice with complete memory usually spend more time studying new objects, but mice usually distribute attention more evenly between the two objects, indicating memory dysfunction.

The researchers then enhanced the brain’s waste drainage by treating some mice through therapy that stimulates lymphatic vessel growth. The results showed that mice with revived lymphatic vessels were more interested in new subjects than those of untreated mice, a sign of improving memory function.

“Functional lymphatic system is crucial for brain health and memory,” King said. “Therapies that support the health of the human waste management system may have health benefits for natural brain aging.”

These findings provide a novel view of brain health. Most neurological treatments focus on crossing the blood-brain barrier to directly affect brain tissue. Instead, this approach targets drainage systems outside the brain, potentially circumventing the need for drug penetration, such a protective barrier.

When the lymphatic system is damaged and waste accumulates in the brain, the responsibility for cleaning up is transferred to microglia (the resident immune cells of the brain). But these local cleaning staff ended up being overwhelmed.

The study showed that these spawned cells emit distress signals in the form of an immune protein called interleukin 6 (IL-6). This protein appears to disrupt normal brain function by creating imbalances in neuronal signaling.

Specifically, the study found that elevated IL-6 levels reduce inhibitory signals, often acting like noisy headphones in the brain’s communication network. This disruption changes brain wiring and function impaired.

Interestingly, when the researchers improved lymphatic vessel function in older mice, IL-6 levels decreased and restored the brain’s noise reduction mechanism—and improved memory performance.

This approach represents a paradigm shift that some neuroscientists believe to be in solving neurological diseases. Rather than trying to repair damaged neurons directly, increasing waste removal may optimize the function of surviving brain cells.

“As we mark the tenth anniversary of the discovery of the brain’s lymphatic system, these new findings provide insight into the importance of the system to brain health,” Kipnis said. “Targeting more accessible lymphatic vessels located outside the brain may prove to be an exciting new area. We may not be able to revive neurons, but we may be able to ensure their optimal functioning by regulating the regulation of meningeal lymphatic vessels.”

The study is also based on previous work by the Kipnis team, showing that certain experimental Alzheimer’s treatments work more effectively in mice when combined with treatments that improve brain fluid and debris.

The current research has been supported by funding from the National Institute of Aging and other organizations, adding to growing evidence that the body’s waste management system plays a crucial role in maintaining brain health throughout life.

Although these findings are still preliminary and limited to mouse models, they propose potential new directions for developing therapies to address age-related cognitive decline and possibly neurodegenerative diseases in humans – not only on the brain itself, but also on support systems that support their cleaning and function.

As researchers continue to explore this emerging field of neuroimmunology, the relationship between the brain’s waste-treatment system and cognitive function can reshape methods for treating a range of neurological diseases that currently have limited treatment options.