Researchers created a multidimensional, molecular map of how the mouse brain develops after birth and how it reacts to inflammation. The findings show that some of the molecular programs that govern brain development can be reactivated in the brain during inflammation.

Brain development is a complex process involving the precise diversification and distribution of cells into distinct areas. Karolinska Institutet and Yale University researchers developed a new method called spatial tri-omics, which enables them to simultaneously measure in a specific area of the brain: the activity of genes, how this activity is regulated by epigenetic changes, and if this activity ultimately leads to the production of proteins. The study is based on analyses of mouse and human brains at different stages of development.

Myelination is the process that provides nerve cells with a protective sheath of insulating myelin that ensures the quick and effective transmission of nerve signals. An area of the brain with abundant myelination is the corpus callosum, which is affected by neurological diseases such as multiple sclerosis, where myelin and oligodendrocytes (the myelin-producing cells) are attacked by the immune system.

Using a mouse model that disrupts myelination in specific areas in the brain, the researchers found that the brain’s immune cells, microglia, are activated not only locally as a response to damage, but also at remote sites of the brain.

One important finding was that genetic programs that are activated during brain development can be reactivated in neuroinflammation.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers noted that it can provide clues as to how and why the myelin is broken down by diseases such as MS. They found that inflammation in the brain can spread and affect areas far from the original locus of damage, which could offer insights into how MS develops and provide new tools for treating the disease.

The study was is published in the journal Nature.