How can a zebrafish help solve the mystery of hereditary brain diseases?

The zebrafish or Danio rerio is a small tropical freshwater fish. It reproduces easily, with a short breeding cycle, fertilization and development in vitro, transparent embryo body, and 87 percent high homology with human genes, all of which allow for further observation and screening of developmental changes, eventually may preventing the occurrence of human diseases. Given the advantages of zebrafish, scientists tend to favor them.

By delving into the rapidly developing zebrafish embryos, scientists can better understand the underlying foundations of brain-compounding diseases, including autism and schizophrenia.

Researchers at Ohio State University are interested in understanding neurodevelopmental changes caused by genetic defects associated with neurological diseases-especially the loss of Protocadherin-19 or PCDH19. The link between genetic mutations and brain diseases is recognized, but the mechanism by which one mutation may cause another mutation has been a mystery.

Their new study, published online in eNeuro, points to "aggregation" in the brain that may disrupt normal developmental and healthy cellular interactions.

Scientists have discovered hundreds of genes that cause schizophrenia, autism, and other brain diseases, but no one knows what causes these gene mutations. So researchers at Ohio State University aim to understand the cellular effects of these genes and how defects can cause changes in brain development.

Lead researcher James Jontes and his collaborator Sarah Light used high-power microscopes to see what happened to neurology when they knocked out PCDH19 in zebrafish embryos. Researchers can observe changes in cell levels over time.

Neurons form a network in the brain that is vital to human development, thought, function, behavior, and emotion. In the altered zebrafish, the researchers were able to observe neuronal levels of activity in great detail.

With the help of advanced mathematical analysis aimed at finding the relationship between neurons and their patterns of activity, they found that the zebrafish with this mutation had a tighter, denser neural network than the normal zebrafish brain.

We saw a lot of correlation between the neurons of the mutant zebrafish. We don't know exactly what this means, but it may mean that abnormal connections between cells usually do not interact. When too many cells are incorporated into the neural network, it may become a problem.

This is the first study to use functional imaging at the single cell level to explore the effects of mutations known to cause neurological diseases in living organisms and to find significant differences in the brain structure of mutant animals.

This type of work has the potential to help us understand more about the relationship between genes and diseases, including autism and epilepsy. We don't fully understand the effects of these mutations on the structure and development of human brains, but if we can figure out how these mutations affect the brain structure and development of zebrafish, we may be closer to the answer, which may be an important step in better treatments.

Cite this article

CUSABIO team. How can a zebrafish help solve the mystery of hereditary brain diseases?.


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