"A better understanding of the brain mechanisms in autism opens up hope for the development of new treatments"

In recent years there has been great progress in the study of the genetics of autism and it has been found that mutations in many dozens of genes are involved in autism and other neurodevelopmental disorders. These findings raised questions about what these genes have in common and how they affect the brain. In a new study recently published in Nature Communications, the role of one of the distinct genes for autism called POGZ was examined

In recent years there has been great progress in the study of the genetics of autism and it has been found that mutations in many dozens of genes are involved in autism and other neurodevelopmental disorders. These findings raised questions about what these genes have in common and how they affect the brain. In a previous study in the laboratory of Prof. Shagiv Shipman from the Institute of Life Sciences and the Center for Autism at the Hebrew University of Jerusalem It was found that the thing that distinguishes a large part of the genes related to autism is their involvement in controlling the activity of many other genes, which are particularly active in three areas of the brain - the cortex (brain cortex), the striatum (subcortical part of the brain) and the cerebellum (cerebellum). The cerebellum plays a central role in the coordination of motor activity, and recently there is growing evidence that it also participates in the development of cognitive and social activity. Therefore, understanding the activity of the cerebellum and the genes that affect it could help in understanding the mechanisms involved in autism, and possibly also lead to new ways of treatment.

In a new study recently published inNature Communications. We will examine the role of one of the distinct genes for autism called POGZ. The choice of this gene was not accidental - Prof. Shipman was interested in POGZ because in humans mutations in this gene are known to cause significant developmental delay and more specifically, in children with a mutation in the POGZ gene, it was found that although some of them are diagnosed on the autism spectrum, they tend to behave in an oversocial manner. They took part in the new study Prof. Shagiv Shipman Together with Prof. Yosef Yarom From the Institute of Life Sciences and the Brain Research Center of the Hebrew University, AndDoctoral students Reut Soliman-Lavi and Ben Teitel, in collaboration with international laboratories. The researchers examined how a mutation in the POGZ gene in mice affects development the brain, and also on the behavior and function of cerebellum.

In the study, the researchers created a mouse model that has a mutation of the gene in the brain. They followed the behavior and development of the mice in order to find out the effect of the genetic change in them, and found that the mutation affects the social and cognitive behavior in the mice in a similar way to that observed in humans who have a mutation in POGZ. Also, in general, the researchers found that the mutation in the gene causes the mice to be overly sociable, impair their learning ability, and delay their growth.

Specifically, the researchers found that the POGZ gene plays a significant role in the creation of brain nerve cells. In the developing brain, the number of cells that divide and produce additional cells is of great importance, as well as the timing at which they stop dividing and differentiate into different types of nerve cells. It was also discovered that POGZ participates in the control of cell division. A mutation in this gene causes an increase in the number of cells that stop dividing and differentiate into nerve cells, a situation that ultimately causes there to be fewer cells in the brain. This finding could explain why some children with a mutation in this gene have microcephaly (an extremely small head circumference). The researchers also found that the mutation reduces the generation of nerve cells in one of the only sites in the brain where there is generation of nerve cells in the adult brain.

Another specific role found for the POGZ gene is regulation of other genes. In the research it was found that the protein encoded by the POGZ gene can silence the expression of various genes, meaning that the gene serves as a kind of off switch for other genes. Accordingly, it was found that a mutation in the POGZ gene caused many genes to change their expression in the brain, and many of them showed an increase in activity because of the mutation in POGZ. Among the genes that changed, there was a clear representation of genes that are known to be related to autism.

In addition, the researchers found that in the cerebellum The number of genes that changed was three times greater compared to another region of the brain that was examined. It was also found that damage to the POGZ gene in the brain of the model animal affects the normal activity of nerve cells in the cerebellum. The researchers performed an electrical recording from Purkinje cells - nerve cells that transmit the output of the cerebellar cortex to the central nervous system. The recording showed that there is a significant decrease in the electrical activity in the Purkinje cells following a mutation in POGZ. That is, the information that goes to the central system is damaged and as a result there are changes in brain activity.

In conclusion, the mutation in the gene affects both the development and the function of the brain, especially the cerebellum. Currently there are no effective drugs to treat the main symptoms of autism, but Prof. Yarom and Prof. Shipman It is believed that their research work and findings may contribute to finding new ways to develop drugs to treat autism, by changing the neural circuits in the cerebellum. Previous studies in the laboratory of Prof. Yarom They showed that it is possible to change the pattern of neural activity in the cerebellum by different chemical substances. In a follow-up study, the researchers will be interested in testing whether there is a possibility to return the mice to behave normally by changing the activity of the cerebellum.

"The work on this particular gene that causes autism and significantly affects brain function gives us new hope for the possibility of discovering a drug that will help children with autism," concludes Prof. Shipman and Prof. Yarom adds: "A better understanding of the brain mechanisms in autism opens up hope for the development of treatments new ones".

Link to research 

More of the topic in Hayadan:

• Research has discovered what happens in the brains of children with autism when they sleep
• Researchers at Tel Aviv University: many genetic mutations that characterize autism and intellectual disability also appear in the brains of Alzheimer's patients
• Researchers have developed a treatment that may prevent developmental delay and autism