‘Miniature Brains’ Reveal An Outsized Secret About Autism

Scientists hoping to uncover the origins of autism have grown a passel of miniature proto-brains in a lab, using reprogrammed skin cells to rewind the clock to the brain’s earliest days of development. From these small creations have come potentially big insights into autism, a diabolically complex disorder.

Peering into the “organoids” they created — clusters of embryonic brain cells smaller than one-tenth of an inch across — the authors of the new research were able to observe that as the autistic brain is under construction, it overproduces the brain cells that act to quiet the cacophony of neural activity in the brain.

The result, compared with a typically-developing brain, is that the developing brain of a child who would go on to develop autism has an imbalance of excitatory and inhibitory neurons. That, said Yale physician and neurobiologist Flora Vaccarino, is a subtle but potentially powerful difference that may help pinpoint at least one bit of faulty wiring that leads to autism’s behavioral symptoms.

The new research was published this week in the journal Cell.

Vaccarino and her colleagues go on to report that when they suppressed a single gene that was abnormally active in organoids created from patients with autism, the researchers were able to correct the imbalance between neurons that quiet cellular impulses and those that amplify them.

The research has many hurdles to surmount before it might be used to diagnose and treat autism when a baby is still in utero, or just after birth, said Vaccarino. But, she added, the idea that their organoids may have given up a key secret of autism’s cause “could give us something to focus on in developing treatments.”

While the insights into autism generated by the new research may be important, the methods used by Vaccarino and her colleagues are quite novel as well. First, the scientists used new lab procedures that have been shown to make skin cells revert to an undifferentiated form, like those harvested from embryos. The study authors then nudged the resulting stem cells to start the process of building a brain, and incubated the result for a month or more.

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