As reported in PressReleasePoint, Researchers at the University of Sheffield have found a clue to the cause of a set of rare neurological disorders known as leukodystrophies- an issue with nerve cell destruction while in the fetus. While the mother is still pregnant, patients were found to already have faulty immune cells, known as microglia, which are responsibility for cleaning out dying neuron cells in the brain. In particular, almost half of our neurons are wiped out during pregnancy, which is the most intensive time of brain development. The dysfunction of microglia during pregnancy contributes to these neurological diseases which are characterized by serious mental and physical deficits.
Leukodystrophies are rare metabolic diseases caused by gene mutations, progressing over time. While all are due to abnormalities in the myelin sheath, the conditions differ based on which part of the myelin sheath is affected. The early symptoms become apparent in the first year of life, and new features develop or worsen with age. They can cause difficulty and loss of movement, sight, hearing, balance, eating, thinking, memory loss, and behavior issues. Less than 1 in 10,000 people are born with these diseases. There are not many treatment options, and the disorders are ultimately fatal in many cases.
Research Spots Issues During Pregnancy
The researchers used transparent zebrafish to study brain development with the disease, where they observed the early onset of the neurological impediment. Typically this defect presents quite differently in animal brains from our own, not causing the same difficulty with movement and brain abnormalities as in humans. This time though, the experimenters were able to replicate the human form in transparent zebrafish such that it modeled the same symptoms as a human patient. Here they observed that the issue was with the microglia. Dr. Noémie Hamilton, a researcher on the study, said
“We found that in our zebrafish model of human leukodystrophy, deficient microglia failed to digest dying neurons. Cells digest their content using their lysosomes which are an acidic cellular compartment used as a recycling factory. We showed that our zebrafish model had lysosomal defects, blocking microglia from performing normally.”
This, she explained, caused inflammation which damaged the brain extremely early in development. They hope from here to study which therapies or medications could be implemented at this early stage to prevent the degeneration. She hopes these unique explanations of the how the disease first takes root can pave the way to news ideas for treatment.