Why do some people stay mentally healthy in childhood but become more prone to brain diseases like dementia as they grow older?
A team of researchers from KAIST (Korea Advanced Institute of Science and Technology) has uncovered an important part of the answer.
Their study found that a certain “switch” in the brain’s support cells—called astrocytes—plays a key role in how the brain’s immune system responds later in life.
Astrocytes are the most common support cells in the brain, helping maintain healthy brain function. The researchers discovered that a gene called NR3C1, which helps produce a receptor for stress hormones (glucocorticoids), controls this switch.
The gene acts during a short period after birth to limit how much inflammation astrocytes can cause in the brain later in life. If this gene doesn’t do its job properly in early life, it can leave the brain more vulnerable to diseases like Alzheimer’s and multiple sclerosis in adulthood.
The research was led by Professor Inkyung Jung from KAIST’s Department of Biological Sciences and Associate Director Won-Suk Chung from the Institute for Basic Science. Using advanced methods in mice, the team tracked how astrocytes change as the brain develops.
They studied how the DNA in these cells folds and which parts of the DNA control key genes. They found that 55 special proteins called transcription factors help guide how astrocytes mature. Among them, NR3C1 was the most important.
Interestingly, mice without this gene in their astrocytes appeared healthy at first. But when they were exposed to a model of multiple sclerosis—a condition where the immune system attacks the brain and spinal cord—the mice had worse symptoms. Their astrocytes reacted too strongly, causing extra inflammation.
The researchers found that when NR3C1 is missing during early development, it changes how immune-related genes in astrocytes are set up. These genes become more “open” and ready to react to threats, even if the threat is mild.
This means the brain becomes more sensitive to inflammation as the person ages. In other words, NR3C1 acts like a brake early in life to prevent immune overreactions later.
“This is the first time we’ve shown that astrocytes’ immune behavior is shaped by a memory built early in life,” said Professor Chung. “This could help explain how conditions like Alzheimer’s begin.”
Professor Jung added, “We found a time window in early life where brain support cells are programmed in a way that affects health decades later. Learning how this works might help us create new treatments for brain diseases caused by immune system problems.”
The study was published on September 22 in the journal Nature Communications. The first authors were Dr. Seongwan Park and PhD student Hyeonji Park.
If you care about dementia, please read studies about Dizziness upon standing may be linked to dementia risk and findings of Scientists find the ties between high blood pressure and dementia.
For more about dementia, please read studies about Early heart rhythm problem linked to higher dementia risk and findings of Green leafy vegetables may help reduce Alzheimer’s risk.
The study is published in Nature Communications.
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