The findings, published in the journal Nature after a decade of research, may one day pave the way for scientists to design treatments that advance these stages of brain development intact.
This 20-year study suggests that one cause of autism may be a delicate imbalance between two types of neurons in the brain’s cerebral cortex, which are responsible for higher-order processes such as thinking. I’m digging into the previous theory. Emotions, decision making, and language.
Some neurons in this area of the brain excite other neurons, causing them to fire. Other cells called interneurons do the opposite. Excessive excitement can impair the brain’s ability to concentrate and lead to epilepsy, a seizure disorder more common in people with autism than in the general population. Therefore, scientists believe that more inhibitory interneurons are needed to maintain the proper balance.
In the developing fetus, these nerve cells begin deep in the brain in an area called the subcranial region and then slowly migrate to the cerebral cortex. The process begins during the second trimester and ends during the infant’s second year of life, said Serge Pasqua, a professor of psychiatry and behavioral sciences at Stanford University who led the study.
Professor Paska’s team, which includes researchers from the University of California, San Francisco and the Icahn School of Medicine at Mount Sinai, examined 425 genes associated with neurodevelopmental disorders to determine which genes interfere with the generation and migration of interneurons. Ta. Among the genes identified in the study were genes associated with autism.
“What’s really great about this paper is that autism is a collection of different behaviors that we don’t have. [an] We were able to understand how these behaviors are related to differences in the brain,” said James, a professor of child psychiatry and psychology at Yale School of Medicine who was not involved in the study.・Mr. McPartland said.
This new study advances autism research by “starting to deepen our fundamental understanding of the components of brain development,” he said.
A new way to screen for autism genes
For ethical reasons, it is not possible to observe developmental stages. Processes that occur in the fetal brain.
Scientists can often learn about the role an individual gene plays by observing what happens when that gene is knocked out of cells in a laboratory dish. But it will take time for him to knock out each of the 425 genes one by one.
For the study, Pasca and his colleagues used a technology they developed six years ago that allows them to test all 425 genes at once. They engineered the cells so that only the neurons that suppressed the firing of other neurons glowed green. They also used the gene editing system CRISPR to create different cells lacking one of the 425 genes.
The scientists created clumps of cells that modeled the structure and function of the brain’s subcranial and cerebral cortex. Next, two different clumps were placed side by side in a laboratory dish.
“We found that as soon as we brought them close together, they fused together,” Pasca said. “And the cells know exactly what to do and invade the cortex exactly as they do in humans.”
It’s even more remarkable because in living brains, the area under the pallium that makes interneurons is not right next to the cerebral cortex, but several inches away, Pasca said.
Pasca et al. allowed time for interneurons to form and migrate to the cerebral cortex. Next, they looked at the genetic profiles of the different cells. This allowed him to look for genes that cause two defects: failure to generate interneurons and failure to migrate interneurons to the cerebral cortex.
They discovered 13 genes whose absence prevented interneuron formation. They identified 33 additional genes that, when deleted, prevent interneurons from migrating to the cerebral cortex. Overall, 46 genes, or 11 percent of the 425 genes associated with neurodevelopmental disorders, appear to affect neurons that suppress neighboring neurons, causing an imbalance.
Researchers learned that LNPK, one of the genes important for interneuron migration, is associated with seizure disorders. This supports the idea that seizures result from too much excitation and too little inhibition of neurons.
Researchers used clumps of fused cells to “diagnose autism” [neurodevelopmental disorder] Genes,” Guo-li Ming, a professor in the Department of Neuroscience and Psychiatry at the University of Pennsylvania, wrote in an email commenting on the study.
Min is not involved in the project, which could one day lead researchers to develop treatments for autism and other disorders based on an individual patient’s genetic profile. He said it was a “masterpiece.”
autism services cliff
Experts emphasized that autism is not a single disease, but a set of disorders. Neuronal imbalance is only one of several possible causes.
For example, many people with autism have defects in microglia, cells that control brain development, injury repair, and maintenance of networks that process information.
He also said that genes alone cannot explain autism. McPartland of Yale University. “It’s complex, and it’s fascinating. You can have [autism in] They are identical twins and in most cases both have autism. But not always. “
Jennifer Singh, an autism expert and associate professor in Georgia Tech’s Department of History and Sociology, says too much money has been poured into exploring the genetic basis of autism spectrum disorders. Stated.Shin pointed out 2018 report According to a federal advisory committee, 60 percent of funding for autism research deals with biology and risk factors, but only a small amount deals with “lifespan issues” for people living with various disabilities. It turned out to be 2%.
“This hyper-focus and massive investment obscures the real issues facing autistic people and their families,” Singh wrote in an email. She referred to the “autism services cliff” that prevents people with autism from attending public schools. “Services that help adults with autism don’t exist or are no longer available,” she said.
“It’s important to study the natural history of this disease,” Pasca said. But if we want to develop effective methods, we also need to understand the biological basis. [treatments]”
