Potential Implications for Parkinson’s Disease in Study of How Estrogen Controls Brain Inflammation in Birds

Researchers at American University in Washington, D.C. studied the rapid response that takes place in the brains of zebra finches in response to trauma and found that estrogen, produced by glial cells in the brain in response to injury, has the ability to control excessive inflammation.

These findings might represent a new approach to control excessive brain inflammation, a condition that has neurodegenerative effects and is associated with many conditions such as Parkinson’s disease.

The research results were presented by study leader Prof. Colin Saldanha at the annual meeting of the Society for Neuroscience in Washington, D.C. The research by Saldanha’s group has been funded for more than a decade by the U.S. National Institutes of Health because of its potential application in treating neurodegenerative diseases.

While inflammation is a vital and normal part of the body’s immune response, it affects the brain in a different way when compared to other parts of the body. Research has shown that chronic and excessive inflammation is linked to neurodegeneration, leading to cell damage and neuronal death in areas of the brain that control movement and memory.

After a brain injury, controlling excessive inflammation is imperative to preserving brain function. Saldanha, a neurobiologist and member of AU’s Center for Behavioral Neuroscience, and his team have been studying the role of estrogen in inflammation using songbirds as animal models due to their brain plasticity, among other reasons. Like humans and other animals, songbirds also produce estrogen in their brains.

Previous research has shown how hormones communicate with neurons through a new method called synaptocrine signaling, in which neurons create and feed higher levels of estrogen to each other. Moreover, researchers have discovered that, following brain injury, glial cells — non-neuronal cells with vital functions in the nervous system — synthesize estrogen.

The team focused on the rapid estrogen response observed in the brains of songbirds because the release of estrogen in the brain to control inflammation happens within 24 hours, while in mammals this process takes place over several days, which can lead to failing to protect against neurodegeneration. The results revealed that glial cells activated the rapid response in the brains of songbirds.

The team induced acute injury in the animals, which caused inflammation via cytokine release, and observed that the estrogen response was controlled by preventing a key protein, aromatase, from working.

First, researchers injured both sides of the brain, but exposed only one side with estrogen, which showed less inflammation. Then they injured both sides of the brain and limited aromatase function to only one side of the brain. On the side without aromatase, inflammatory cytokines remained dangerously elevated.

These results reveal that estrogen controls inflammation and its production happens in response to brain injury. “We can’t just pump people full of estrogen. It can have very bad effects on systems other than the brain. It’s very tricky, which is why exploring this is so important, so we can figure out how to harness its power without any deleterious side effects,” Saldanha concluded.