Gyrus with autism

Brain-like Organoids help uncover the causes of autism at the molecular level

Tatiana Matveeva "Scientific Russia"

Scientists from the University of Utah (USA) have grown in the laboratory an organoid resembling a brain gyrus, which is formed in a predictable way (it can be reproduced).

The organoid makes it possible to identify differences that may contribute to the development of autism, reports EurekAlert!. A study describing organoids and their potential for understanding neural diseases is published in Nature Communications (Wang et al., Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes).

Creating a model of the brain, the researchers turned human stem cells into neuroepithelial cells – a special type of stem cells that form self-organizing structures. Within a few months, these structures combined into spheres and increased in size and complexity at about the same rate as in the developing brain of a growing fetus.

After five months in the laboratory, the organoids resembled "one gyrus of the human brain" 15-19 weeks after conception. The structures contained many nerve and other types of cells found in the cerebral cortex–the outermost layer of the brain involved in speech, emotions, reasoning and other higher mental processes.

Organoids self-organized in a predictable way, forming neural networks that generated a variety of electrical signals characteristic of various types of mature brain cells.

These organoids, which more reliably reflect the complex structures of the cortex, will allow scientists to study how certain types of cells arise in the brain and work together to perform more complex functions.

The team used an innovative process to study the consequences of a genetic anomaly associated with autism spectrum disorder and the development of the human brain. They found that organoids designed to have lower levels of SHANK3 gene expression had certain features.

Despite the fact that the organoids looked normal, some of their cells were not functioning properly. The neurons turned out to be hyperactive, they were more often excited in response to stimuli. Other signs indicate that neurons may inefficiently transmit signals to other neurons. Specific molecular pathways that cause cells to stick to each other have been disrupted.

These results help to uncover the causes of autism-related symptoms at the cellular and molecular level, the authors say. They also demonstrate that lab-grown organoids will be useful for better understanding the brain, how it develops, and what goes wrong during illness.

"One of the goals is to use brain organoids to test drugs or other interventions aimed at eliminating or treating disorders," the authors say. 

Portal "Eternal youth" http://vechnayamolodost.ru