Researchers at Karolinska Institutet in Sweden and Yale University in the United States have developed a groundbreaking multidimensional map that details the development of the mouse brain post-birth and its response to inflammation. The findings, published in the journal Nature on November 5, 2025, reveal that specific molecular programs responsible for brain development can be reactivated during inflammatory responses.
The study highlights the complexity of brain development, which involves the precise distribution and diversification of cells across various regions. To achieve their results, the researchers introduced a novel technique termed spatial tri-omics. This method enables simultaneous measurement of gene activity, the regulation of this activity by epigenetic changes, and the production of proteins within a defined area of the brain.
Gonçalo Castelo-Branco, a professor at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, explained, “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.”
One significant aspect of brain function is myelination, a process that provides nerve cells with a protective myelin sheath, facilitating rapid signal transmission. The corpus callosum, known for its high myelination, is often implicated in neurological disorders like multiple sclerosis (MS), where myelin and oligodendrocytes, the cells that produce myelin, are attacked by the immune system.
Through experiments using a mouse model that disrupts myelination, the researchers discovered that the brain’s immune cells, known as microglia, are activated not only in response to local damage but also at distant sites within the brain. Rong Fan, a professor at Yale University and co-leader of the study, remarked, “We were surprised to see that inflammation can spread to other parts of the brain, even when there’s no direct damage there. This suggests that in the event of disease, the brain has a complex means of communication between its different areas.”
The researchers also identified that genetic programs activated during brain development can be reactivated during instances of neuroinflammation. Professor Castelo-Branco noted, “This is interesting as it can give us clues as to how and why myelin is broken down by diseases like MS. We found that inflammation in the brain can spread and affect areas far from the original locus of damage, which could give insights into how MS develops and provide us with new tools for treating the disease.”
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 in the United States.
The paper, titled “Spatial dynamics of brain development and neuroinflammation,” features contributions from various scientists, including postdoctoral fellows Di Zhang at Yale University and Leslie Kirby at Karolinska Institutet, who are co-first authors of the study.
This research represents a significant step forward in understanding the interplay between brain development and inflammation, with potential implications for the treatment of diseases like multiple sclerosis.
