The blood-brain barrier may contribute to neurological disorders by doing more than blocking molecules. A new study suggests the barrier also changes how neurons work. Damage to it already shows up in Alzheimer’s and other brain-wasting diseases. So the barrier may play a bigger role in how these disorders develop.
Summary: Early studies show the BBB is damaged in people with brain-wasting disorders like Alzheimer’s. Until now, researchers saw the BBB as just a barrier. But a new study suggests the BBB can change how neurons work. So it may play a bigger role in how these disorders develop.
Brain disorders like Alzheimer’s, Parkinson’s and many others are on the rise. Yet doctors and researchers have struggled to explain what causes them.
More than a century of research has failed to answer many key questions. So researchers have lately changed their approach. They think one reason studies have not explained conditions like dementia is too much focus on neurons. In recent years, researchers have turned to other brain cells. They have focused a lot on glial cells, which support and adjust neurons. Glial cells also play a vital role in the brain’s immune defense and inflammation.
Now a new study in the Proceedings of the National Academy of Sciences (PNAS) shows a new way the blood-brain barrier (BBB) may be contributing to the rise of these neurological disorders. Science has long known the BBB exists. It has also known the BBB is damaged in people with conditions like Alzheimer’s or Parkinson’s. But until now, researchers assumed these BBB changes came second, after the disease process.
For decades, researchers made some simple assumptions. One was that the BBB is just a barrier to certain substances. They thought of it like the doorman at a fancy restaurant or bar. It only lets certain kinds of molecules into the brain. But now researchers say the BBB has a bigger say in how the brain works. What if it does not just let certain molecules in, but also shows them the way? What if it actively directs their traffic and so changes how neurons work? That is exactly what the new study suggests.
The new study suggests the BBB can act as a filter and change how neurons work. After letting certain molecules into the brain, it can also guide where they go. That shapes how neurons work. Researchers used fruit fly larvae for the study. Their BBB is much like that of mammals but simpler to study. In the fruit fly, special glial cells act as the BBB, much like lining cells in animals with backbones.
In the study, researchers focused on enzymes called metalloproteinases, since these enzymes can interact with glia and neurons. Using a special technique, they found something called Notch signaling. This signaling happens in both fruit flies and humans. The researchers say they did not plan to study Notch. But they found it played a vital role in keeping the BBB intact. Notch signaling helps hold the whole BBB structure together. When the Notch signal was blocked, the BBB broke down. So this signaling pathway can affect the basic workings of the nervous system. It can even affect the release of certain brain chemicals.
They also found that, under certain conditions, Notch signaling could change how neurons fired, even with the BBB intact. That showed the BBB is not just a barrier. It can also shape how the brain works. It also means BBB breakdown might play a bigger role in brain disorders. Researchers say a broken BBB does not just mean a leaky barrier. It also means changes in how the brain works.
The idea that the BBB can shape how neurons work is brand new. Researchers say these findings point research in a new direction. The role of the BBB in Alzheimer’s and other brain problems must now be studied with these findings in mind.
So far, very little is known about the role of Notch signaling and metalloproteinases in the human brain. So they need more study. Better understanding of the BBB will also help us understand brain-wasting disorders and find treatments that work.
Frequently asked questions
What is the blood-brain barrier and its purpose?
The blood-brain barrier (BBB) is a wall of special cells between the blood and the brain. For decades, researchers saw it as a simple gate, like a doorman at a busy restaurant who only lets certain molecules in. A study in the Proceedings of the National Academy of Sciences (PNAS) suggests it does more. After letting molecules in, it can also guide where they go and shape how neurons work.
Is blood-brain barrier damage linked to Alzheimer’s and Parkinson’s disease?
Yes. Doctors have long known that the blood-brain barrier is damaged in people with Alzheimer’s, Parkinson’s and other brain-wasting disorders. Researchers assumed that damage came second, after the disease had started. The newer work suggests the barrier may play a bigger role in how these disorders develop. A breakdown means more than a leak. It also changes how the brain works.
Can the blood-brain barrier change how the brain works?
The study points that way. Researchers worked with fruit fly larvae, whose barrier is like the mammal version but simpler to study. They found that a pathway called Notch signaling helps hold the barrier together. When Notch was blocked, the barrier broke down. Under certain conditions, Notch signaling also changed how neurons fired, even with the barrier intact. It can also affect the release of some brain chemicals.
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