Tuesday , June 28 2022

Testosterone activates risk genes for autism


The boy is sitting alone at the water. / mizina, stock.adobe.com

Researchers have found an explanation for the higher risk of autism in boys. / mizina, stock.adobe.com

Heidelberg – Autism occurs 4 times more often in boys than girls. For the first time, researchers from the Department of Molecular Humane Ethics at the University Hospital in Heidelberg have found an explanation: their studies on human cells and brain areas of mice showed that male hormone testosterone significantly activates certain risk genes in the brain before and after birth. The results were i Boundaries in Molecular Neuroscience published (2018; doi: 10.3389 / fnmol.2018.00337).

So far, it has only been known that defects in these specific genes are a strong risk factor for the development of neuronal developmental disorders. The new results indicate that these genetic defects may have a greater impact on the brain in male than female subjects.

"Now we have a first indication why – boys have a significantly higher risk of autism than girls, at least in relation to an important group of the many risk genes," says senior author Gudrun Rappold, director of the Department of Molecular Genetic Genetics.

The tests in their group showed that some genes called SHANK 1, 2 and 3 in the young brain of male mice are increasingly translated into proteins and that this is affected by higher levels of sex hormone testosterone. Heidelberg's research team has been researching SHANK genes for several years, as defects in these parts of genetic information play an important role in the development of autism and other mental illnesses.

More testosterone – more skank protein

For the test, the team used a cell culture of childhood brain tumors (neuroblastoma) as a model for developing nerve cells. The researchers discovered in these cells that activation of SHANK genes is dependent on the binding of testosterone to an androgen receptor. When this receptor was blocked, the strong activation of the risk genes disappeared. "We could confirm this in studies in brain areas of young mice where this androgen receptor did not form: they were significantly activated weaker than in control animals with intact receptors," explains Simone Berkel, this study together with doctoral student Ahmed Eltokhi.

The researchers also studied the amount of brain protein in the brain of young male and female mice before and after birth. In male animals, which naturally have more testosterone in the blood and brain, significantly higher levels of Shank proteins were found than in women. "We believe that the greater amount of skinn protein in the male brain increases the" blow "of defects in the SHANK genes, thus leading to a higher risk of autism," concludes Rappold.

In autism, the development of nerve cells in the brain interferes. One in 68 children (approximately 1.5%) is affected. The typical symptoms are noticeable early, so the diagnosis is usually made before the third life. Autistic people have difficulty in social interaction, communication and perceptual processing and often display intense, special interests and abilities as well as repetitive and narrow (restrictive) behavioral patterns. However, these characteristics of autistic behavior can vary widely from patient to patient – you are therefore talking about an autism spectrum. © IDW / Energie / Aerzteblatt.de

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