Lab-Grown Mini Brains Shed Light on Autism


Scientists exploring the intricacies of social disorders – including behavioral conditions like autism – found compelling evidence of neural short-circuiting in miniature brains they grew in the lab.

These so-called mini brains, which are only five millimeters wide, or roughly the size of a red ant, are grown from stem cells contained in children’s teeth and can develop up to six layers of cerebral cortex, which is the outer layer of a human brain.

Stem cell research. Credit: FDA photo by Michael J. Ermarth/Wikimedia Commons

A group of researchers at the University of California, San Diego led by Dr. Alysson Muotri developed two sets of mini brains from the stem cells of children with developmental disorders.

On one side, the group used stem cells from children with autism and Rett syndrome, two conditions associated with difficulties in social behavior and communication. The researchers developed a second set of mini brains using stem cells from children with Williams syndrome, a condition that’s marked by extremely high sociability.

The researchers wanted to find out whether they could pinpoint changes in brain activity between the two sets of mini brains, which retain characteristics of a living, human brain.

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“Though they’re not as well defined as they are in a real brain, they resemble what you find in an embryonic fetus,” Muotri told New Scientist.

The researchers discovered a significant pattern. In the mini brains grown from the stem cells of children with autism and Rett syndrome, they found noticeably dampened neural activity. Among those grown from Williams syndrome, they saw much different activity – namely, a significantly higher amount of neural connections than normal.

“The differences are striking, and go in opposite directions,” said Muotri.

Mini brains grown from the stem cells of children without any behavioral conditions had neural activity in a range between the two. The researchers believe the study using mini brains provides clear evidence of early brain development and its impact on disorders related to social functioning.

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Boy with autism. Credit: Scott Vaughan/Wikimedia Commons, CC BY-2.0

“In Williams syndrome, one of the cortical layers makes large projections linking into many other layers, and these are important for sociality,” said Muotri. “By comparison, autism-linked brains are more immature, with fewer synapses.”

These fluctuating levels of neural activity appear to persist over the course of a person’s lifetime. Muotri and his team performed autopsies on deceased individual with these behavioral conditions and found “similar patterns” in their brains compared to those found in the lab-grown mini brains.

Expanding on Mini Brain Research

Previously, Muotri’s lab found that autism is linked to over-sized brains that appear to occur due to “cellular pathway dysregulation” and “altered” brain networks.

A tissue culture dish mounted under a microscope for viewing by a technician. Credit: Linda Bartlett/Wikimedia Commons

Muotri and his colleagues also discovered that the hyper-sociable Williams syndrome is caused by the deletion of only 25 of the more than 30,000 genes in the human brain. The study involving mini brains “fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain,” notes a related article in Nature.

The mini-brain experiments are key to studying early brain development, and the researchers can shed light on future treatment options. Muotri noted that some scientists have begun clinical trials on gene-based treatment for Rett syndrome.