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Study finds brains with autism fail to trim synapses

by PAM BELLUCK New York Times News Service on August 22, 2014 10:34 AM

As a baby’s brain develops, there is an explosion of synapses, the connections that allow neurons to send and receive signals. But during childhood and adolescence, the brain needs to start pruning those synapses, limiting their number so different brain areas can develop specific functions and are not overloaded with stimuli.

Now a new study suggests that in children with autism, something in the process goes awry, leaving an oversupply of synapses in at least some parts of the brain.

The finding provides clues to how autism develops from childhood on, and may help explain some symptoms like oversensitivity to noise or social experiences, as well as why many people with autism also have epileptic seizures.

It could also help scientists in the search for treatments, if they can develop safe therapies to fix the system the brain uses to clear extra synapses.

The study, published Thursday in the journal Neuron, involved tissue from the brains of children and adolescents who had died from ages 2 to 20. About half had autism; the others did not.

The researchers, from Columbia University Medical Center, looked closely at an area of the brain’s temporal lobe involved in social behavior and communication. Analyzing tissue from 20 of the brains, they counted spines — the tiny neuron protrusions that receive signals via synapses — and found more spines in children with autism.

The scientists found that at younger ages, the number of spines did not differ tremendously between the two groups of children, but adolescents with autism had significantly more than those without autism. Typical 19-year-olds had 41 percent fewer synapses than toddlers, but those in their late teenage years with autism had only 16 percent fewer than young children with autism.

One child with autism who was 3 when he died had more synapses than any of the typical children of any age, said David Sulzer, a neurobiologist and senior investigator of the study.

Experts said the fact that young children in both groups had roughly the same number of synapses suggested a clearing problem in autism rather than an overproduction problem.

“More is not better when it comes to synapses, for sure, and pruning is absolutely essential,” said Lisa Boulanger, a molecular biologist at Princeton who was not involved in the research. “If it was overgrowth, you’d expect them to be different from the start, but because the synapse difference comes on so late, it’s probably pruning.”

Sulzer’s team also found biomarkers and proteins in the brains with autism that reflected malfunctions in the system of clearing out old and degraded cells, a process called autophagy.

“They showed that these markers of autophagy decrease” in autism-afflicted brains, said Eric Klann, a professor of neural science at New York University. “Without autophagy, this pruning can’t take place.”

The findings are the latest in an area of autism research that is drawing increasing interest. For years, scientists have debated whether autism is a problem of brains with too little connectivity or too much, or some combination.

Ralph-Axel Mller, a neuroscientist at San Diego State University, said there was growing evidence of overconnectivity, including from brain imaging studies he has conducted.

“Impairments that we see in autism seem to be partly due to different parts of the brain talking too much to each other,” he said. “You need to lose connections in order to develop a fine-tuned system of brain networks, because if all parts of the brain talk to all parts of the brain, all you get is noise.”

More synapses also create opportunity for epileptic seizures because there are more electrical signals being transmitted in the brain, Klann said. More than a third of people with autism have epilepsy.

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