When babies are born their brains surge with tremendously fast growing new synapses, the connections that allow neurons to send and receive signals. As babies grow into children and adolescents, the rapid growth of synapses slows down and a new process called pruning reduces the number of synapses so the different regions of the brain can develop more specialized functions and are not be overwhelmed by stimuli. At least in most brains, 0n August 21st, 2014 neuroscientists from Columbia University Medical Center (CUMC) published in the journal Neuron which found that this process of synapse pruning does not take place to the same scale and effectiveness in autistic children.
According to the NY Times the study’s findings provide clues to how autism develops from childhood on, and may help explain some common symptoms like oversensitivity to noise or social experiences, as well as why many people with autism have epileptic seizures.
[caption id="attachment_650" align="alignnone" width="300"] Neurons in brains from people with autism do not undergo normal pruning during childhood and adolescence. The images show representative neurons from unaffected brains (left) and brains from autistic patients (right); the spines on the neurons indicate the location of synapses. (Image credit: Guomei Tang, PhD and Mark S. Sonders, PhD/Columbia University Medical Center)[/caption]
During normal brain development, a burst of synapse formation occurs in infancy, particularly in the cortex, a region involved in autistic behaviors; pruning eliminates about half of these cortical synapses by late adolescence. Synapses are known to be affected by many genes linked to autism, and some researchers have hypothesized that people with autism may have more synapses.
To test this hypothesis, co-author Guomei Tang, PhD, assistant professor of neurology at CUMC, examined brains from children with autism who had died from other causes. Thirteen brains came from children ages two to 9, and thirteen brains came from children ages 13 to 20. Twenty-two brains from children without autism were also examined for comparison.
Dr. Tang measured synapse density in a small section of tissue in each brain by counting the number of tiny spines that branch from these cortical neurons; each spine connects with another neuron via a synapse.
By late childhood, she found, spine density had dropped by about half in the control brains, but by only 16 percent in the brains from autism patients.
“It’s the first time that anyone has looked for, and seen, a lack of pruning during development of children with autism,” Dr. Sulzer said, “although lower numbers of synapses in some brain areas have been detected in brains from older patients and in mice with autistic-like behaviors.”
In addition to the finding that children with autism had less pruning as compared to the control group, researchers also published findings relating to the use of a drug, Rapamycin, a possible therapy to incomplete pruning.
Rapamycin restores normal synaptic pruning can improve autistic-like behaviors in mice, the researchers found, even when the drug is given after the behaviors have appeared.
Although the drug, rapamycin, has side effects that may preclude its use in people with autism, “the fact that we can see changes in behavior suggests that autism may still be treatable after a child is diagnosed, if we can find a better drug,” said the study’s senior investigator, David Sulzer, PhD, professor of neurobiology in the Departments of Psychiatry, Neurology, and Pharmacology at CUMC.
[caption id="attachment_651" align="alignnone" width="300"] David Sulzer, a neurobiologist at Columbia, led a study that may help explain symptoms of autism like oversensitivity to noise, as well as why many people with autism also have epilepsy. PC NY Times.[/caption]
One of the problems with Rapamycin however, is that has very serious side effects. According to the NY Times experts and the authors cautioned that it was much too early to know if a drug like rapamycin, an immunosuppressant with potentially serious side effects, could be used successfully in people with autism. The condition can only be approximated in mice, so the study results may not translate to humans. And the mice studied had a rare genetic disease that accounted for a fraction of autism disorders.
“We don’t know if it’s this particular flavor of autism,” Dr. Boulanger a molecular biologist at Princeton who was not involved in the research. “This drug has really horrible side effects, and you don’t want to give it to everybody.”
But even though the drug may not be a treatment for people, the research gives hope that another therapy might be found to correct the pruning problem in childhood or adolescence, after autism symptoms emerge.
“The pruning problem seems to happen later in development than one might think,” Dr. Eric Klann, a professor of neural science at New York University said. “It suggests that if you could intervene in that process that it could be beneficial for social behavior.”