Researchers from Karolinska Institutet in Sweden and Yale University in the United States have created a comprehensive molecular map detailing the development of the mouse brain post-birth and its response to inflammation. Published in the journal Nature on November 5, 2025, this groundbreaking study reveals that certain molecular programs governing brain development can be reactivated during inflammatory responses.
The brain’s development is a multifaceted process that includes the precise organization and distribution of various cell types across distinct regions. The researchers introduced a novel method called spatial tri-omics, which allows them to measure three critical aspects in specific brain areas: gene activity, the regulation of this activity by epigenetic changes, and the resultant protein production. This approach enables a detailed analysis of both mouse and human brains at various developmental stages.
Gonçalo Castelo-Branco, a professor at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, stated, “We’ve been able to use this multidimensional method to track brain development over time and map changes from birth to a young age in different parts of the brain, as well as study how the brain reacts to inflammation.”
Understanding Myelination and Neuroinflammation
Myelination, the process by which nerve cells are insulated with myelin, is crucial for efficient nerve signal transmission. The corpus callosum, a brain area rich in myelination, is significantly impacted by neurological disorders such as multiple sclerosis (MS). In MS, the immune system attacks myelin and oligodendrocytes, the cells responsible for myelin production.
Using a mouse model designed to disrupt myelination in specific brain regions, the researchers discovered that microglia, the brain’s immune cells, are activated not only at the site of damage but also in distant areas of the brain. “We were surprised to see that inflammation can spread to other parts of the brain, even when there’s no direct damage there,” explained Rong Fan, a professor at Yale University and a lead researcher on the study. “This suggests that in the event of disease, the brain has a complex means of communication between its different areas.”
One of the study’s important findings is that genetic programs activated during brain development can be reactivated during neuroinflammation. According to Castelo-Branco, “This is interesting as it can give us clues as to how and why the myelin is broken down by diseases like MS.” The researchers found that inflammation in the brain can propagate and influence areas far from the initial site of damage, providing insights into the progression of MS and potential new treatment strategies.
Funding and Contributors
The research was supported by several funding bodies, including the Swedish Research Council, the Swedish Brain Foundation, the Knut and Alice Wallenberg Foundation, the EU’s Horizon Europe programme, and the National Institutes of Health (USA). Postdoctoral fellows Di Zhang at Yale University and Leslie Kirby at Karolinska Institutet served as co-first authors of the paper.
As the understanding of brain development and inflammation deepens, this research paves the way for new insights into neurological diseases. The findings not only enhance the scientific community’s grasp of brain dynamics but also open avenues for potential therapeutic interventions in conditions such as multiple sclerosis.
