Scientists have found a clue to how autism spectrum disorder disrupts the brain's information highways.
The problem involves cells that help keep the traffic of signals moving smoothly through brain circuits, a team reported Monday in the journal Nature Neuroscience.
The team found that in both mouse and human brains affected by autism, there's an abnormality in cells that produce a substance called myelin.
That's a problem because myelin provides the "insulation" for brain circuits, allowing them to quickly and reliably carry electrical signals from one area to another. And having either too little or too much of this myelin coating can result in a wide range of neurological problems.
For example, multiple sclerosis occurs when the myelin around nerve fibers is damaged. The results, which vary from person to person, can affect not only the signals that control muscles, but also the ones involved in learning and thinking.
The finding could help explain why autism spectrum disorders include such a wide range of social and behavioral features, says Brady Maher, a lead investigator at the Lieber Institute for Brain Development and an associate professor in the psychiatry department at Johns Hopkins School of Medicine.
"Myelination could be a problem that ties all of these autism spectrum disorders together," Maher says. And if that's true, he says, it might be possible to prevent or even reverse the symptoms using drugs that affect myelination.
"If we get to these kids really early, we might be able to change their developmental trajectory and improve their outcomes," Maher says.
"It's possible to make these cells healthier," adds Dr. Daniel Weinberger, director of the Lieber Institute and a professor at Johns Hopkins. "And it's never been a target of treatment in autism."
The study adds to the evidence that myelination problems are present in "several developmental disorders and in particular in autism," says Dr. Flora Vaccarino, a professor in the neuroscience department at Yale who was not involved in the research.
It also shows how one faulty regulatory system in the brain can lead to either too much myelination or too little, she says. And that may help explain why people with autism spectrum disorders may have brains that are either unusually large or unusually small.
Researchers involved in the study came upon the myelination problem while looking for something else.
They were studying brain cells in mice with a gene mutation that causes Pitt-Hopkins syndrome, which can include features of autism spectrum disorder. "We saw a signature that suggested there might be something wrong with myelination," Maher says. "So that was pretty surprising to us."
More experiments confirmed that "there was a clear deficit," in the cells that control myelination, which are called oligodendrocytes, he says. This was true not only in mice with the Pitt-Hopkins syndrome, but in other mouse models of autism, too.
Next, a biostatistics expert named Andrew Jaffe looked at a genetic analysis of brain tissue from people with autism who had died. And that experiment also found problems with the system that controls myelination.
To fully understand what's going on though, the problem needs to be studied in developing brain tissue, Vaccarino says.
That should be possible, she says, using tiny clusters of human brain cells called brain organoids, which can be grown in a petri dish. Vaccarino's lab has created brain organoids from the cells of people with autism spectrum disorder, which might reveal how the myelination problems begin, she says.
Brain myelination "really does not start in earnest until the first year or two of life," Weinberger says. "And this is around the time that autism is first apparent."
That might eventually mean a treatment that corrected a problem with myelination could help children who are diagnosed early in life, he says. Several such treatments are being developed to treat people with multiple sclerosis, a disease that erodes myelin.
SCOTT SIMON, HOST:
Autism spectrum disorder has multiple causes and a wide range of symptoms. But scientists say they found a brain abnormality that seems to exist in all people with the disorder. NPR's Jon Hamilton reports that the finding, if it holds up, could lead to new treatments.
JON HAMILTON, BYLINE: Autism has been linked to everything from genetic mutations to infections during pregnancy. Yet many scientists think the brains of people with autism must have something in common, something that accounts for symptoms like social difficulties and repetitive behaviors. Brady Maher is a researcher at the Lieber Institute for Brain Development in Baltimore.
BRADY MAHER: The idea is that there is some kind of common pathway that is leading to this disorder.
HAMILTON: And Maher is part of a team that thinks they've found one. The discovery came while they were studying a rare gene mutation. It causes something called Pitt-Hopkins Syndrome.
MAHER: Children that have this mutation have autistic features. They have communication deficits and repetitive behaviors.
HAMILTON: The team noticed that in mice, this mutation seemed to affect a substance called myelin. Myelin is what insulates the nerve fibers that carry electrical signals in the brain. Maher, who is also on the faculty at Johns Hopkins University, says at first, the team had doubts about their discovery.
MAHER: This was such a strong signal that we just had to go and see if this was true. And so we just started to do experiments. And sure enough, there was a clear deficit.
HAMILTON: A deficit involving the cells that produce myelin. And that made the team wonder whether myelin might be a problem in other forms of autism. So they studied several mouse models of the disorder. Dr. Daniel Weinberger, who directs the Lieber Institute, says the mice confirmed their hunch.
DANIEL WEINBERGER: They seemed to have, also, an abnormality in the development and function of these very specific cells which make this lining of the nerve fibers.
HAMILTON: But mice don't get autism. So the team studied the brains of people on the autism spectrum using tissue taken during autopsies. And Weinberger says, once again, there were problems with the cells that produce myelin.
WEINBERGER: That was surprising because this had never previously been seen to be a common feature of all these different forms of autism.
HAMILTON: But he says the explanation makes sense.
WEINBERGER: This process of laying down myelin in the human brain really does not start in earnest until the first year or two of life. And this is around the time that autism is first apparent.
HAMILTON: If the cells that make myelin really are a big factor, it might offer a new approach to treatment. Scientists are already working on drugs to reverse the loss of myelin in people with multiple sclerosis. And Brady Maher says this sort of drug might also help children with autism.
MAHER: If we could get to these kids really early and begin treatment as soon as we diagnose this, that might be a critical window that we could really sort of change their developmental trajectory and improve their outcome.
HAMILTON: But first, scientists will need to confirm the link between autism spectrum disorder and myelin. Then they'll need to figure out how to tweak cells that make the substance in just the right way. Dr. Flora Vaccarino at Yale School of Medicine says that will be tricky because autism varies from child to child.
FLORA VACCARINO: In children with autism, you have some children that have a very large brain and some children that have a normal or smaller brain.
HAMILTON: So it could be that some kids are making too much myelin and others too little. Also, Vaccarino says, the brain's own system for regulating substances like myelin is a wonder.
VACCARINO: It's actually so complex that it's almost unfathomable to sort of think about, how is it done just right?
HAMILTON: Let alone try to fix the process when it's gone wrong. The myelin study appears in the journal Nature Neuroscience. Jon Hamilton, NPR News.
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