Autism Linked to Excess of Synapses

A normal process in which unneeded connections between the brain’s neurons die off may go awry in autistic children, a Columbia University research team found.

After studying the postmortem brains of 20 autistic children (all of whom had died of other causes) the researchers saw that by late childhood, the numbers of synapses had not declined as quickly than in samples of brain tissue in a control group.

In a study reported online Aug. 21 in the journal Neuron and on the Simons Foundation Autism Research Initiative website Sept. 4, senior investigator David Sulzer, PhD, and colleagues suggest the finding could explain some autism symptoms.

Infant brains produce a huge burst of synapses, billions of connections. Normal “pruning” of these synapses begins in childhood and by adolescence about half are gone.

Researchers have a drug, rapamycin that has been shown to work to do that in mice with an autism-like condition. The drug reverses these rodents’ anti-social behaviors. But it has side effects that may preclude human use, Sulzer noted.

Still, the fact that eliminating the extra synapses meant a change in behavior is promising. “Autism may still be treatable after a child is diagnosed if we can find a better drug,” Sulzer said

The scientists are also focusing on a protein called mTOR. It spurs cells to produce more proteins and grow larger. Children with autism have unusually high levels of mTOR, which apparently interferes with synaptic pruning.

In the research, the scientists counted the numbers of dendritic spines in the autistic brains and the control group. They found that by adolescence spine density decreased by only 16% in the brains of deceased teens who had autism compared with a 45% decrease in the control group.

When they looked at mTOR activity, they saw that there no difference in the amount of the protein in the two groups during early childhood (age 2 to 9) but that in adolescence, the autistic brains had higher levels of mTOR than the control group.