Neurodegenerative diseases are a well-known problem worldwide, as well as the cause of most dementia cases. Alzheimer’s disease, Parkinson’s disease, and many more, all of these eventually (with age) lead to the decline of neural function of the affected person. As of right now, there’s no real cure, only ways to slow down or stop the progression, and even that isn’t the case for all conditions. So, is there any way we could reverse the neurodegeneration?
It actually appears so! Scientists are looking into meningeal lymphatic vessels and their role in neural and behavioral changes. It has been previously discovered that they, in fact, play a role in various neurodegenerative conditions, as they serve as an outlet for cerebrospinal fluid, however, the exact mechanisms were still unclear. So what now?
The study used both surgical and genetic models, which ended up showing that disruption of meningeal lymphatic function reduced inhibitory synaptic transmission and impaired memory performance, similarly to in disease scenario. Microglia were identified as key mediators of the synaptic changes, and there was also increased cortical interleukin 6 expression (which can be associated with neuroinflammation, and thus contribute to said changes). Multiple types of deletion of interleukin 6 led to improvement in the inhibitory synaptic balance, further proving its role in the mentioned changes.
In the end, enhancing meningeal lymphatics and their function in aged mice, where vessels are naturally compromised, reversed aging-associated synaptic and behavioral alterations (which can be linked to neurodegenerative diseases). Together, these findings reveal a microglia-dependent mechanism, tying meningeal lymphatic dysfunction to altered synaptic balance and cognitive decline.
This discovery altogether gives potential to further study the meningeal lymphatics and their effects in the cortical circuitry in correlation with interleukin 6-dependent mechanisms and find a potential target to develop new treatment options for age-related cognitive decline.
Resources:
Kim K., et al. (2025) Meningeal lymphatics-microglia axis regulates synaptic physiology.
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