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.”

Pig fat has made the leap from kitchen staple to laboratory marvel for its ability to grow bone. Stem cells from the fat tissue of Yucatán minipigs grew into pieces of bone that were then successfully implanted into the pigs’ jaws, researchers report June 15 in Science Translational Medicine.

The team of bioengineers used cow bone scaffolds infused with stem cells from a minipig’s fat tissue to grow bone grafts in a special chamber in the lab. The new bones, which were personally fitted to each minipig’s jaw, fared better after six months than standard bone grafts not seeded with fat cells.

The new research brings scientists a step closer to one day using fat stem cells to repair humans’ broken or worn-out body parts.

Busy nerve cells in the brain are hungry and beckon oxygen-rich blood to replenish themselves. But active nerve cells in newborn mouse brains can’t yet make this request, and their silence leaves them hungry, scientists report June 22 in the Journal of Neuroscience.

Instead of being a dismal starvation diet, this lean time may actually spur the brain to develop properly. The new results, though, muddy the interpretation of the brain imaging technique called functional MRI when it is used on infants.
Most people assume that all busy nerve cells, or neurons, signal nearby blood vessels to replenish themselves. But there were hints from fMRI studies of young children that their brains don’t always follow this rule. “The newborn brain is doing something weird,” says study coauthor Elizabeth Hillman of Columbia University.

That weirdness, she suspected, might be explained by an immature communication system in young brains. To find out, she and her colleagues looked for neuron-blood connections in mice as they grew. “What we’re trying to do is create a road map for what we think you actually should see,” Hillman says.

When 7-day-old mice were touched on their hind paws, a small group of neurons in the brain responded instantly, firing off messages in a flurry of activity. Despite this action, no fresh blood arrived, the team found. By 13 days, the nerve cell reaction got bigger, spreading across a wider stretch of the brain. Still the blood didn’t come. But by the time the mice reached adulthood, neural activity prompted an influx of blood. The results show that young mouse brains lack the ability to send blood to busy neurons, a skill that influences how the brain operates (SN: 11/14/15, p. 22).

That finding was enabled by technology that allowed the researchers to see neural activity and blood flow at the exact same time. It’s “a powerful application of cutting-edge imaging techniques,” says neuroscientist Alan Jasanoff of MIT.

Showing that oxygen demands are unheeded during early development is interesting, says neuroscientist Matthew Colonnese of George Washington University School of Medicine and Health Sciences in Washington, D.C. More studies are needed to say whether human infant brains behave similarly and, if so, how this process might sculpt the brain.

The results don’t mean that fMRI data from young children aren’t valuable, Hillman says. “What we are begging people to do is to make room for this hypothesis, and actually treat it as an opportunity.” Blood flow data might not be a good proxy for neural activity in newborns, but “it may well be measuring a change that is very important to normal brain development,” she says.