Children with autism have extra brain synapses

New research has shown that children with autism have a very high number of synapses - connections between neurons in the brain. So researchers have developed a new drug that promotes synaptic pruning, and reverses autistic-like behaviour in mice.

Children with autism have extra synapses in their brain due to a slowdown in the normal brain "pruning" process during development, say US neuroscientists.

They found a drug that restores synaptic pruning also reverses autistic-like behaviours in mice, they report in the journal Neuron.

"We were able to treat mice after the [disorder] had appeared," says study co-author neurobiologist David Sulzer of Columbia University Medical Center.

The findings suggest the condition could one day be treated in teenagers and adults, "though there is a lot of work to be done," he says.

The work is "extremely exciting", says Professor Ralph-Axel Mueller of San Diego State University, who was not involved in the research.

A synapse is where one neurone communicates with another.

With too many synapses, a "brain region that should be talking only to a select number of other regions is receiving irrelevant information from many others," explains Mueller, who has done pioneering work in over-connectivity.

During brain development, a burst of synapse formation occurs in infancy, particularly in the cortex, a region involved in autistic behaviours; pruning eliminates about half of these cortical synapses by late adolescence.

For the new study, the researchers painstakingly counted synapses in a key region of the cortex of 26 children and adolescents aged between 2 and 20 with autism who had died from other causes. They compared that to 22 brains from children without autism that were donated to science.

In the autistic brains, synaptic density was more than 50 per cent higher than that in the brains of children without autism and sometimes two-thirds greater.

"It's the first time that anyone has looked for, and seen, a lack of pruning during development of children with autism," says Sulzer, "although lower numbers of synapses in some brain areas have been detected in brains from older patients and in mice with autistic-like behaviours."

Over-connectivity

It is not clear if too many synapses are the main reason for autism, but many genes linked to autism play a role in synapse pruning. And the discovery that synapse pruning reversed autistic behaviour in the lab mice suggests over-connectivity may be key.

The researchers traced the pruning effect to a protein called mTOR. When mTOR is overactive brain cells lose much of their self-trimming ability.

"Almost all of our human subjects had overactive mTOR and decreased autophagy, and all appear to have a lack of normal synaptic pruning," says Sulzer.

To restore normal synaptic pruning and reverse autistic-like behaviours in mice, the researchers administered rapamycin, an immunosuppressant drug that prevents organ rejection and inhibits mTOR.

However, even if the findings are confirmed -- and Sulzer notes that treatments that work in lab animals often fail in people -- it is unlikely that rapamycin would be used in people with autism because its widescale immune-suppressing effects would likely cause serious side effects.

"But there could be better drugs," says Sulzer "such as a molecule that dials up production of synapse-pruning proteins."

One remaining puzzle is how the mice's brains, or the drug, know which synapses to keep and which to prune.

"But the mice started behaving normally" after receiving the synapse-pruning drug, "which suggests the right ones are being pruned," says Sulzer.