Neuron: Human Brain Immune Cells Mature Hundreds of Times More Slowly Than Those in Mice

Scientists have identified a human-specific gene variant that causes immune cells in the brain to mature unusually slowly—over a period of years. This prolonged maturation may be linked to some of the human brain’s remarkable cognitive abilities. The study was published in the journal Neuron.

The research focuses on microglia, specialized immune cells that make up around 5–10% of all cells in the brain. They not only protect neural tissue but also help “fine-tune” the brain by determining which connections between neurons should be preserved and which should be eliminated. This process plays an important role in shaping the neural networks of the developing brain.

Researchers led by Carlos Díaz-Salazar of Columbia University’s Zuckerman Institute, working in Frank Polleux’s laboratory, compared microglial maturation in humans and mice. They found that in mice, these cells fully mature in just about three weeks, whereas in humans the process takes approximately four to eight years.

The key to this difference appears to be a human-specific version of a gene called SRGAP2. Its specialized copies, which are absent in other species, are almost ten times more active in microglia than in neurons, and they appear to slow down the cells’ maturation.

According to the researchers, the unusually prolonged maturation of microglia may be critical for building the complex neural networks underlying human intelligence. Slowly maturing cells may have more time to fine-tune and refine connections in a child’s developing brain.

The SRGAP2 gene has previously been linked to distinctive features of the human brain, but its specific role in microglial function has been demonstrated for the first time in this study. Notably, the gene is also active in neurons, but its specialized copies are significantly more active in the brain’s immune cells.

The discovery could help scientists better understand the cellular mechanisms that distinguish the human brain and may shed light on neurodevelopmental disorders such as autism and schizophrenia, in which this delicate process of neural fine-tuning may be disrupted.