The Secret to Young Memory: Brain Drain May Be the Key
- Lidi Garcia
- Apr 1
- 3 min read
The lymphatic vessels that help cleanse the brain may play an important role in memory function. When these vessels malfunction, neural connections in the brain become unbalanced, impairing memory and reasoning. This happens because a cell in the brain’s immune system, called microglia, produces more inflammatory chemicals, such as interleukin-6 (IL-6). Scientists have shown that blocking this chemical or improving the function of these vessels can restore memory in mice, suggesting a possible way to combat brain aging and diseases such as Alzheimer’s.
Our brains produce waste products that need to be eliminated in order for them to function properly. This cleaning is done, in part, by the meningeal lymphatic vessels, which are located in the outermost layer surrounding the brain, called the dura mater.
These vessels help drain cerebrospinal fluid (CSF), carrying the waste products to the lymph nodes in the neck.
Previous studies have shown that when these vessels do not function properly, diseases such as Alzheimer's and brain injuries worsen, while strengthening them can improve memory and healthy aging in mice.
However, it was not yet known exactly how this affected the functioning of neurons and the balance of brain connections.
To better understand this relationship, scientists at Washington University in St Louis, USA, used genetically modified mice and surgical techniques to impair the function of these lymphatic vessels.
They found that this altered the balance between excitatory and inhibitory electrical signals in the brain. This balance is essential for information processing in the brain, and its imbalance is associated with several neurological diseases, such as schizophrenia, autism and Alzheimer's.
In mice with dysfunctional lymphatic vessels, there was a reduction in inhibitory transmission, which impaired the animals' memory and cognitive ability. The team also identified that microglia, a type of cell in the brain's immune system, plays a central role in this process.
When the lymphatic vessels do not function well, microglia begin to produce more interleukin-6 (IL-6), an inflammatory molecule that interferes with the functioning of neural connections. To confirm this, the researchers blocked the action of IL-6, either by removing the gene responsible for its production or by applying specific medications.
The result was that the balance of brain connections was restored and memory performance improved in the mice.
In addition, the scientists tested whether strengthening the lymphatic vessels could reverse the problem. They applied this treatment to elderly mice, which naturally have weakened lymphatic vessels.
The results showed that restoring lymphatic function improved brain connections and memory, suggesting a potential path to combating age-related cognitive decline.
These findings suggest that malfunctioning meningeal lymphatic vessels may contribute to cognitive problems by affecting the balance of neural connections through IL-6. In the future, therapies that strengthen these vessels or block IL-6 could help treat neurodegenerative diseases and improve brain health during aging.
The image shows how the brain’s drainage system can affect memory. On the left side, when the meningeal lymphatic vessels are functioning properly, brain waste is eliminated correctly, keeping the microglia (the brain’s defense cells) healthy and balanced. This helps preserve memory. On the right side, when these vessels are dysfunctional, waste builds up and activates the microglia in a harmful way, increasing the production of the molecule IL-6. This unbalances the signals between neurons and can lead to memory problems. In other words, keeping the brain’s drainage system healthy may be essential to preventing cognitive decline.
LEIA MAIS:
Meningeal lymphatics-microglia axis regulates synaptic physiology
Kyungdeok Kim, Daviti Abramishvili, Siling Du, Zachary Papadopoulos, Jay Cao, Jasmin Herz, Igor Smirnov, Jean-Leon Thomas, Marco Colonna, and Jonathan Kipnis
Cell. March 21, 2025
Abstract:
Meningeal lymphatics serve as an outlet for cerebrospinal fluid, and their dysfunction is associated with various neurodegenerative conditions. Previous studies have demonstrated that dysfunctional meningeal lymphatics evoke behavioral changes, but the neural mechanisms underlying these changes have remained elusive. Here, we show that prolonged impairment of meningeal lymphatics alters the balance of cortical excitatory and inhibitory synaptic inputs, accompanied by deficits in memory tasks. These synaptic and behavioral alterations induced by lymphatic dysfunction are mediated by microglia, leading to increased expression of the interleukin 6 gene (Il6). IL-6 drives inhibitory synapse phenotypes via a combination of trans- and classical IL-6 signaling. Restoring meningeal lymphatic function in aged mice reverses age-associated synaptic and behavioral alterations. Our findings suggest that dysfunctional meningeal lymphatics adversely impact cortical circuitry through an IL-6-dependent mechanism and identify a potential target for treating aging-associated cognitive decline.
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