[ad_1]
Careful examination of the rapidly growing zebrafish embryo helps neuroscientists better understand the potential causes of brain disorders, including autism and schizophrenia.
Researchers at Ohio State University wanted to understand the changes in neurological development resulting from a genetic abnormality badociated with a neurological disease, including the loss of a gene called Protocadherin-19 or PCDH19. The link between mutation and brain disorders is well established, but the mechanics of why one could lead to the other was a mystery.
The new study, published online this month in the journal in Euro, indicates a "clustering" of cellular interactions in the brain that can disrupt normal development and brain health.
Scientists have discovered hundreds of genes responsible for schizophrenia, autism and other brain disorders, but nobody really knows what's wrong with these genetic mutations. "
The principal investigator, James Jontes, badociate professor of neuroscience at Ohio State and member of the Institute of Neurology of the University
"Our goal is to understand the cellular roles of these genes and how abnormalities can lead to changes in brain development."
The zebrafish, or Danio rerio, are small tropical freshwater fish that attract scientists for a handful of reasons. Their embryos are transparent, they develop at a blistering speed and share a large part of the DNA with people, allowing a timely and enlightening review of developmental changes that could potentially have consequences in an attempt to thwart human disease.
Jontes and her badociate, graduate student Sarah Light, wanted to see what was happening neurologically when they introduced a zebrafish PCDH19 mutation.
With the help of a powerful microscope that allowed researchers to track the evolution of the cellular level – an instrument made by Jontes himself – researchers found a clear difference between embryonic development in "wild" zebrafish and embryonic zebrafish in which they had been eliminated. the PCDH19 gene.
"This is the first study to use functional imaging at a cell level to explore the effects of a mutation known to cause a human neurological disease in a living organism." We also found obvious differences in the brain architecture of the animals carrying the mutation, "says Jontes.
"This type of work is likely to help us to understand more fully the relationships between genes and diseases, including autism and epilepsy.We do not understand exactly what these mutations do for the structure and the brain development in humans and if we can determine what they do in fish, it will take us a long way to answers. "
Neurons form networks in the brain that are essential for human development, thought, function, behavior, and emotions. In the modified zebrafish, the researchers were able to observe in a very detailed way the activity at the neuron level.
And, with the help of an advanced mathematical badysis designed to look for relationships between neurons and patterns of activity, they found that the neural networks of zebrafish carrying the mutation were more connected than those of the ordinary zebrafish brain.
Data were collected between three and six days after fertilization, a period of rapid growth and maturation in zebrafish. On the sixth day after fertilization, the zebrafish larvae already exhibit behaviors such as hunting for food and swimming.
"We have seen many interconnections between mutant zebrafish neurons – we do not know exactly what this means, but it could mean that inappropriate connections are occurring between cells that would not interact normally. to be that it becomes a problem when too many cells are embedded in a network of neurons ".
Jontes said that neuroscientists are intrigued by the fact that any number of genetic mutations have been linked to a particular disease, such as autism.
Work like this could help explain the impact of each of these mutations on the human disease, which could be an important step towards better treatment, he said.
Source:
State University of Ohio
Journal reference:
Light, S.E.W. & Jontes, J.D. (2019) Multilevel calcium imaging reveals disturbed development of zebrafish network topology pcdh19 Mutants. in Euro. doi.org/10.1523/ENEURO.0420-18.2019.
[ad_2]
Source link
