Testosterone activates the risk genes for autism

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

Heidelberg – Autism is 4 times more common among boys than girls. For the first time, scientists from the Department of Molecular Human Genetics at the Heidelberg University Hospital have found an explanation: their studies on human cells and brain areas of mice have shown that testosterone, a male bad hormone, significantly activates certain risk genes in the brain before and after birth. The results were in Frontiers in Neuroscience Molecular published (2018, doi: 10.3389 / fnmol.2018.00337).

Until now, it was known only that the defects of these specific genes constituted an important risk factor for the development of neuronal development disorders. The new findings suggest that these genetic defects may have a greater impact on the brains of men than women.

"We now have a first indication of the reason – at least with respect to a large group of many genes at risk – that boys are at a much higher risk of autism than girls," says the l & # 39; author Gudrun Rappold, director of the department of human genetics.

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

More testosterone – more protein in the stem

For the tests, the team used a cell culture of childhood brain tumors (neuroblastoma) as a model for developing nerve cells. Scientists have discovered in these cells that the activation of SHANK genes depends on the binding of testosterone to an androgen receptor. When this receptor was blocked, the strong activation of the genes at risk disappeared. "We were able to confirm this in studies on the brains of young mice that did not form this androgen receptor: they were activated much weaker than in control animals with intact receptors," Simone says. Berkel, in collaboration with the doctoral student Ahmed Eltokhi conducted.

The researchers also investigated the amount of stem protein in the brains 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 protein have been observed compared to females. "We believe that the greatest amount of stem protein in the male brain increases the" punch "of defects in SHANK genes and therefore increases the risk of autism," concludes Rappold.

In autism, the development of nerve cells in the brain is disrupted. One in 68 children (about 1.5%) is affected. The typical symptoms are perceptible early, so the diagnosis is usually made before the 3rd year of life. Autistic people have difficulties in social interaction, communication and perception processing and often have intense and specific interests and abilities, as well as repetitive and narrow (restrictive) behavioral patterns. However, these characteristics of autistic behavior can vary considerably from one patient to another – so we are talking about an autistic spectrum. © IDW / energy / aerzteblatt.de