Neurons made directly from skin cells model autism mutations

Skin cells taken from mice with an autism-linked mutation and transformed directly into neurons have the same properties as neurons from the brains of these mice. The study, published 8 October in Proceedings of the National Academy of Sciences, validates an efficient technique to study disease-linked mutations¹.

To study the effect of autism-linked mutations on neurons, researchers often create induced pluripotent stem (iPS) cells from skin or blood cells, returning them to a primitive state from which they can become any cell in the body. Expressing a cocktail of three to four genes then sets these iPS cells on the path to neuron development.

In the past two years, researchers have refined an alternative technique that produces neurons directly from skin or blood cells, skipping the reprogramming step.

To confirm the validity of this technique for studying autism, researchers used it to generate neurons from skin cells of mice with an autism-linked mutation. This is a mutation (R704C) in NLGN3, which helps organize connections between neurons. The researchers then compared the effect of the mutation on these neurons with those taken directly from the mouse’s brain.

Both kinds of neurons show the same problems with signaling, the researchers found. They show a decrease in a receptor (AMPA) that responds to activating signals from the chemical messenger glutamate. As a result, these neurons receive fewer activating signals. In a living animal, this would shift the brain’s balance between active and inactive neurons, which researchers have suggested as a mechanism underlying autism.

References:

1: Chanda S. et al. Proc. Natl. Acad. Sci. USA 110, 16622-16627 (2013) PubMed