Autism spectrum disorders (ASD) interfere with the ability to communicate and hinder the social relationships of those affected and for this reason it was thought that the brain changes associated with autism were located in certain areas of the brain related to social behavior and language, however, new research led by scientists at the University of California, Los Angeles (UCLA) has found that the brain changes in autism are comprehensive, affecting the entire cerebral cortex.
The new study has been published in Nature and is a major advance in understanding how ASDs progress at the molecular level, as it has found changes throughout the brain in virtually all of the 11 cortical regions they have analyzed, regardless of whether they are areas of higher critical associations (those involved in functions such as reasoning, language, social cognition, and mental flexibility), or primary sensory regions.
“This work represents the culmination of more than a decade of work by many members of the lab that was required to perform such a comprehensive analysis of the autism brain,” said study author Dr. Daniel Geschwind, Distinguished Professor of Gordon and Virginia MacDonald Human Sciences. Genetics, Neurology and Psychiatry at UCLA.
RNA changes in the brain are likely the cause of ASD, not the result of the disorder
“We are beginning to image the state of the brain, at the molecular level, of the brain in people who had a diagnosis of autism. This provides us with a molecular pathology, which is similar to other brain disorders such as Parkinson’s, Alzheimer’s, and stroke provide a key starting point for understanding the mechanisms of the disorder, which will inform and accelerate the development of disease-altering therapies. ”.
One more step in the development of effective therapies for autism
Autism and other psychiatric disorders lacked a defining pathology and this made the development of more effective therapies more difficult. A little over 10 years ago, Geschwind led the first attempt to identify the molecular pathology of autism, focusing on two areas of the brain: the temporal lobe and the frontal lobe, which were chosen because they are higher-order association regions involved in higher cognition, especially social cognition, which is disrupted in ASDs.
The researchers examined gene expression in 11 cortical regions by sequencing RNA from each of the four major cortical lobes, and compared brain tissue samples obtained after death from 112 people with ASD with healthy brain tissue. Although they observed changes in each cortical region profiled, the largest drop in gene levels was recorded in the visual cortex and the parietal cortex, which processes information such as touch, pain, and temperature.
Researchers have explained that this may reflect the sensory hypersensitivity often found in people with ASD. These experts found strong evidence that the genetic risk for autism is enriched in a specific neural module that has lower expression throughout the brain, indicating that RNA changes in the brain are likely the cause of ASD, and not the result of the disorder.
These scientists now intend to determine whether computational approaches can be used to develop therapies based on reversing the changes in gene expression that the researchers found in ASDs, Geschwind said, adding that researchers can use organoids to shape the changes with the in order to better understand its mechanisms.
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