Saturday , January 23 2021

Testosterone activates risk genes for autism



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

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

Heidelberg – Autism appears four times more often in boys than girls. For the first time, scientists at the Department of Human Molecular Genetics 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 brain before and after birth. The results were in Borders in molecular neuroscience published (2018; two: 10.3389 / fnmol.2018.00337).

Up to now, it was only known that defects in these specific genes are a strong risk factor for the development of neuronal developmental disorders. The new results suggest that these genetic defects may have a greater impact on the brains of male individuals than those of the female.

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

Their group tests have shown that in the younger brains of male mice, certain genes called SHANK 1, 2 and 3 are increasingly translated into proteins and that this is influenced by higher levels of testosterone sex hormone. The Heidelberg research group has been investigating the SHANK genes for years because defects in these sections of genetic information play an important role in the development of autism and other mental illnesses.

More testosterone – more protein

For the tests, the team used a cell culture of brain tumors from childhood (neuroblastoma) as a model for nerve cell development. Scientists have found in these cells that activation of SHANK genes depends on the binding of testosterone to an androgen receptor. When this receptor was blocked, the strong activation of the risk genes disappeared. We have been able to confirm this in studies in brain areas of young mice in which this androgen receptor is not formed: they were significantly weaker activated than in control animals with intact receptors, "explains Simone Berkel , this study together with PhD student Ahmed Eltokhi conducted.

The researchers also studied the amount of prosthetic proteins 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 proteins were found than in females. "We believe that a greater amount of Shank protein in the male brain increases punch defects in SHANK genes and therefore results in a higher risk of autism," Rappold concludes.

In autism, the development of nerve cells in the brain is disturbed. One in 68 children (approximately 1.5%) is affected. Typical symptoms are noticeable early, so diagnosis is usually made before the third year of life. People with autism experience difficulties in social interaction, communication and perceptual processing, and often have intense interests and abilities, as well as repetitive and restrictive behavioral patterns. However, these characteristics of autistic behavior can vary greatly from patient to patient – one speaks of a spectrum of autism. © IDW / energy / aerzteblatt.de


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