Why do some people stay mentally healthy when they are young, but later in life become more likely to suffer from brain disorders like dementia?
A group of scientists in South Korea may have found part of the answer. Their research shows that a certain type of brain cell, called an astrocyte, goes through an important change early in life.
This change can affect how the brain handles inflammation and fights off diseases later in adulthood.
Astrocytes are the most common support cells in the brain. They help keep the brain working properly, and they also play a role in controlling the brain’s immune system. The research, led by Professor Inkyung Jung from KAIST and Professor Won-Suk Chung from the Institute for Basic Science, focused on how these astrocytes develop over time.
The team discovered that a gene called NR3C1 acts like a switch during early brain development. This gene helps control how astrocytes respond to inflammation later in life. The scientists used mice to study how this process works.
They found that NR3C1 plays a key role during a short time after birth, setting up a kind of “memory” in the cells. This memory affects how the cells respond to immune system triggers years later.
To explore this in detail, the scientists used advanced tools to study the 3D structure of DNA in the developing brain. This allowed them to see which parts of the DNA were active and how they were interacting with each other.
They found 55 important “transcription factors”—proteins that turn genes on and off—that guide how astrocytes mature. Among these, NR3C1 stood out as the most important for controlling immune reactions.
Interestingly, removing NR3C1 from astrocytes didn’t seem to harm brain development. The mice grew up normally.
But when the mice got older and were exposed to a disease model that mimics multiple sclerosis, those without NR3C1 had a much stronger immune response. Their brains became inflamed more easily, and they developed more serious symptoms.
This shows that NR3C1 helps calm the brain’s immune system later in life by programming astrocytes early on. Without this “brake,” the immune system can overreact to problems, which may lead to damage and disease.
Professor Won-Suk Chung explained that this is the first time scientists have shown that astrocytes’ immune behavior is shaped by early-life experiences. The team’s discovery gives us new clues about why some people are more likely to develop brain diseases like Alzheimer’s or multiple sclerosis.
Professor Inkyung Jung added that their work also revealed a short time in early development when this switch happens.
Understanding this timing could help scientists find new ways to prevent or treat immune-related brain diseases. If we can learn how to turn this switch back on—or control it in adulthood—we might be able to reduce the risk of brain disorders later in life.
This study highlights how important early life is in shaping brain health for the future. What happens in the first few weeks or months after birth could set the stage for how well our brains cope with stress, disease, and aging decades later.
The study is published in Nature Communications.
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