Leigh syndrome
https://link.springer.com/article/10.1038/s44321-025-00367-4
Leigh syndrome is a rare and serious childhood condition caused by problems in the mitochondria, the tiny structures that give our cells energy. When the brain does not get enough energy, children can lose important skills like walking or talking. Doctors have also noticed that many children show early developmental delays even before brain scans reveal major damage. This study helps explain why these early problems happen. Researchers used mice that carry the same genetic defect seen in many Leigh syndrome patients. These mice lack a protein called NDUFS4, which is needed for a part of the mitochondria called Complex I. Without it, the developing brain cannot make enough energy. Although the mice grew normally in size, their brains were smaller and developed more slowly. The team studied a brain region that produces new cells after birth. In the Leigh syndrome mice, this “cell-making factory” had fewer stem cells, and the remaining ones divided more slowly. The mice also had problems with oligodendrocytes, the cells that make myelin, the coating that helps brain signals travel quickly. As a result, the main connection between the two sides of the brain, the corpus callosum, was thinner. Gene activity analysis showed widespread disruptions in cell growth, energy use, and communication. Overall, the study shows that brain development is affected much earlier than previously thought.