Abnormal sense of touch may play role in autism

In mice, mutations in autism-related genes in skin nerve cells linked to anxiety, poor social skills

diagrams of mouse paths

AROUND AND AROUND  Compared with normal mice, mice that carried a mutated form of the autism-related Mecp2 gene in their peripheral nerve cells avoided the center of an enclosure, a sign of anxiety. 

L. Orefice et al/Cell 2016

Most people think that autism is a disorder of the brain. But the skin may play a role, too, a new study suggests.

Nerve cells in the skin are abnormal in mice with mutations in autism-related genes, leading to poor touch perception, scientists report June 9 in Cell. This trouble sensing touch may influence the developing brain in a way that leads to social deficits and anxiety later in life.

The results raise the provocative idea that fixing abnormal senses may alleviate some of the behavioral symptoms of autism, says study coauthor David Ginty, a neuroscientist at Harvard Medical School.

To explore the role of touch, Ginty and colleagues used mice that carried mutations in genes linked to autism. The genes are active in many places, including the brain. But the researchers used genetic tricks to place the mutated genes only in the peripheral nervous system — the collections of nerves outside the brain and spinal cord.

Adding mutations in a handful of autism-related genes only in peripheral nerves interfered with the mice’s sense of touch. These mice had trouble telling a smooth object from a rough one, and they had outsized reactions to harmless puffs of air. “They’re really touchy when you pick them up,” Ginty says. The sensory breakdown was caused by touch-sensing nerve cells that seemed to have trouble sending messages to the spinal cord, the researchers found.

Some mice also had behavioral deficits. Those with mutations in one of two genes — Mecp2 or Gabrb3 — in the peripheral nervous system, but not the brain, showed more signs of anxiety and interacted with other mice less than mice that didn’t have those mutations. Discovering that changes in the touch-sensing nerve cells could affect behavior was unexpected, Ginty says.  

The skin’s influence seems to be important early in life. Social behaviors and anxiety didn’t suffer when the genes were first mutated in touch-sensing nerve cells during adulthood. The effect on behavior showed up only when the genes were abnormal during development, the team found.

That finding is “the most impressive part of the work,” says neuroscientist Kevin Pelphrey of George Washington University in Washington, D.C. The results emphasize how autism is an inherently developmental disorder, he says.

Pelphrey and colleagues previously found that the brains of children with autism react differently to light touch, which fits with the idea that problems of touch may be involved in the disorder.

Next, Ginty and colleagues plan to figure out exactly when these genes do their important work in the peripheral nervous system. “We are now really interested in the window of time,” he says. “Presumably that window closes at some point, and we’re trying to figure out when that is.” The researchers will also explore ways to restore normal touch sensation, including drugs or genetic manipulations, that would work before the window closes.  

It’s possible that other nerve cells outside the brain are affected in autism, too, says neuroscientist Aaron McGee of the University of Southern California in Los Angeles. “If you have these problems with peripheral nerves that have roles in active sensation, do you also have problems with the nerves that innervate the gut?” If so, that could help explain why people with autism often experience gut trouble. 

McGee cautions that it’s difficult to compare behaviors of mice with symptoms of autism in people. But he says that the genetic experiments described in the paper are “awesome, thorough and significant.”

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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