The brain is a formidable computer and, as any computer, it relies on complex wiring — in the form of synapses — to transmit information. For children with autism, a key issue may be a lack of pruning of the brain's wiring. New research has confirmed that autistic children have an overabundance of synapses in their brains.
While more may seem like a good thing, the surplus is thought to cloud the ability of the brain's synapses to connect and communicate with each other.
A surge of synapses form during infancy, particularly in the cortex, a region linked to autistic behaviors. By late adolescence, about half of these cortical synapses are pruned. The new research by neuroscientists at Columbia University Medical Center (CUMC), confirmed that this process is inhibited in the brains of autistic children. The research also identified a protein called mTOR, which, when overactive, could play a role in the pruning defect.
"This is an important finding that could lead to a novel and much-needed therapeutic strategy for autism," Jeffrey Lieberman, MD, Lawrence C. Kolb Professor and Chair of Psychiatry at CUMC and director of New York State Psychiatric Institute, said in a press release. Kolb was not involved in the study.
To test the idea that autistic brains prune less than normal brains, co-author Guomei Tang, assistant professor of neurology at CUMC, measured synapse density in the brains of deceased autistic children, including 13 brains from children ages two to nine, and 13 brains from children ages 13 to 20. Twenty-two brains from children without autism were also examined for comparison.
Tang measured synapse density in cortical brain tissue samples by counting the tiny spines that extend from neurons. In the control brains, she found that the density of the spines dropped by about half. In the autistic brain samples, they were reduced only by 16 percent.
Taking the research a step further, the team then examined the brains of mice to try and trace the pruning defect. They zeroed-in on a protein called mTOR, which, when overactive, inhibits the brain’s self-trimming ability.
"While people usually think of learning as requiring formation of new synapses, the removal of inappropriate synapses may be just as important," the study's senior investigator, David Sulzer, professor of neurobiology in the Departments of Psychiatry, Neurology, and Pharmacology at CUMC, explained in a press release.
The team then tested the drug rapamycin to try and reverse the effects of the overactive mTOR protein and they found the drug was effective in restoring the brain's pruning behavior even after the symptoms had appeared.
This finding, as well as the fact that large amounts of the overactive protein have been found in the brains of autism patients, lends hope that targeting this protein could be an effective therapy against autism.
Ongoing research on autism has concluded that there are a multitude of genes which contribute to the condition. While a wide range of gene defects may be at play, Sulzer emphasizes that better understanding one of the main potential effects in the brain — a lack of synapse pruning — could offer an key path for treating the condition.
The study was published in the August 21 online issue of the journal Neuron.
Image: The images show representative neurons from autistic (left) and control (right) brains; the spines on the neurons indicate the location of synapses. Credit: Guomei Tang, PhD and Mark S. Sonders, PhD/Columbia University Medical Center