Leigh Syndrome, which is caused by neuronal deaths, and neurological symptoms that are associated with it, are primarily due to microglia. This is the conclusion of a research group from the Institut de Neurociències of the Universitat Autònoma de Barcelona (INc-UAB) in a new study carried out on a mouse model of the disease. Juan Hidalgo, researcher at INc and Department of Cell Biology and Immunology of UAB, coordinated this study and published it in the journal GLIA.
Leigh Syndrome is the most prevalent form of mitochondrial disorder. These diseases are caused by mutations in mitochondrial DNA or mitochondrial RNA. Leigh Syndrome affects organs and tissues that require more energy. It can cause severe motor and respiratory problems for people with it.
Previous studies have shown high levels of neuroinflammation in Leigh Syndrome mouse models. However, it was not known if this had any protective, harmful, or benign effects on the development and progression of the disease. Researchers found that inflammation is responsible for neuronal death. The main culprit was microglia cells. These cells, which normally protect the nervous systems from external or internal aggressions, attack neuronal dysfunction-prone neurons and cause their death.
The study examined the effects of Pexidartinib (PLX-3377) on suppressing microglial cell growth. “With the elimination of microglia it took longer for motor issues to arise, and life expectancy increased. Kevin Aguilar (first author) says that neuronal loss was also less common in these individuals after studying their brains. He adds that although the drug is not an ideal candidate to treat the disease, it has been a key tool for identifying the effects of neuroinflammation and understanding how it occurs.
Study also examined the role of IL-6 in modulating inflammatory activity and guiding microglia activity. We knew that this protein could play a significant role in the syndrome’s symptoms. This is why we wanted an analysis of what happens when there’s a deficiency. Contrary to our expectations, however, respiratory problems were not reduced and the effects were only mild. “This makes us believe that other proteins are involved,” Aguilar says. He concludes, “Our next goal is to determine the exact mechanism by which microglia cells attack neuronal cells and be able to develop more specific treatments in the future.”
The study is a collaboration between both the Neuroinflammation & Oxidative StressThe research group and Mitochondrial NeuropathologyThe INC-UAB laboratory is essential for understanding Leigh Syndrome. It also helps to discover a treatment for mitochondrial disorders, which affect 1 of every 5,000 newborns.