(ORDO NEWS) — Austrian scientists used miniature models of the human brain – organoids – to study a form of autism associated with mental retardation and macrocephaly.
It turned out that the mutation of one gene leads to an earlier and more active formation of neurons, with inhibitory neurons appearing first.
Several hundred genes are associated with autism spectrum disorders. The main symptoms of autism are difficulty with social interaction, limited interests, and frequently repetitive behavioral responses.
Some patients with this diagnosis have mild symptoms, while others may experience serious difficulties during their lives and are almost unable to adapt to society.
One of the genes associated with severe autism is called CHD8. With its mutations, mental retardation and macrocephaly are also often observed – the development of an unusually large brain.
Exactly how CHD8 causes these symptoms has long been unclear. Now scientists from the Institute of Science and Technology of Austria and their colleagues were able to answer this question.
Since mutations in the CHD8 gene affect the brain at a very early stage of development, it is extremely difficult to get a complete picture of the processes it triggers.
In recent years, scientists have been using mice as model organisms to study many human diseases. However, animals with the CHD8 mutation rarely exhibited human-like symptoms. Therefore, some other model was needed.
The authors of the study used organoids, miniature models of organs grown from stem cells. Organoids contain the same types of cells as real organs and allow you to explore their interaction and development in three-dimensional space.
By creating the right conditions, scientists were able to grow brain organelles the size of a lentil grain and reproduce in them the developmental processes that occur with the brain of a human embryo.
Comparisons of models with and without CHD8 mutations showed that mutant organelles grew to large sizes. This was the first confirmation of the validity of the model, since people with the CHD8 mutation often suffer from macrocephaly.
Having obtained samples of all the cells of the organoids, the scientists found that in the mutant models, inhibitory neurons began to form earlier than in the control ones. These nerve cells release neurotransmitters that prevent further signal transmission.
The opposite effect is produced by excitatory neurons, which began to form much later in mutant organelles. In addition, the CHD8 mutation led to the appearance of more dividing cells: they subsequently created a greater number of neurons, which provoked an abnormal increase in the size of organelles.
Further study of organoids will allow us to study in more detail the development of the brain with various genetic pathologies, as well as find new ways to treat and improve the lives of patients.
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