In Autism, Poor ‘Pruning’ of Neurons Leads to Excess Synapses
Children and teens with autism have a sluggish brain “pruning” process during development compared to healthy kids, according to neuroscientists at Columbia University Medical Center (CUMC). This slower pruning process results in a surplus of brain synapses — the points where neurons connect and communicate with one another.
The study, published in the journal Neuron, also found that the drug rapamycin was able to restore normal synaptic pruning and improve autistic-like behaviors in mice, even after symptoms had appeared.
Although rapamycin has side effects that may prevent 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, Ph.D., professor of neurobiology at CUMC.
During infancy, there is an explosion of synapse development, particularly in the cortex, a region involved in autistic behaviors; by late adolescence, about half of these cortical synapses have been pruned away. 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.
For the study, co-author Guomei Tang, Ph.D., 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 nine, and thirteen brains came from adolescents ages 13 to 20. Twenty-two brains from children without autism were also examined for comparison.
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 by a synapse. By late childhood, she found, spine density had dropped to about half in the control brains, but only 16 percent in the brains of those with autism.
“It’s the first time that anyone has looked for, and seen, a lack of pruning during development of children with autism,” 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.”
The researchers found clues that may have caused the pruning defect; the autistic children’s brain cells were filled with old and damaged parts and were very deficient in a degradation pathway known as “autophagy.” Cells use autophagy (a Greek term that means “self-eating”) to break down their own components.
Using a mouse model, the researchers traced the pruning defect to a protein called mTOR. When mTOR is overactive, they found, brain cells lose much of their “self-eating” ability. And without this ability, the brains of the mice were pruned poorly resulting in extra synapses.
“While people usually think of learning as requiring formation of new synapses, ” Sulzer said, “the removal of inappropriate synapses may be just as important.”
The researchers were able to restore normal autophagy and synaptic pruning — and reverse autistic-like behaviors in the mice — by treating them with rapamycin, a drug that inhibits mTOR. The drug was effective even after symptoms had developed.
Because large amounts of overactive mTOR were also found in almost all of the brains of the autism patients, the same processes may occur in children with autism.
Pedersen, T. (2014). In Autism, Poor ‘Pruning’ of Neurons Leads to Excess Synapses. Psych Central. Retrieved on February 12, 2016, from http://psychcentral.com/news/2014/08/23/in-autism-poor-pruning-of-neurons-leads-to-excess-synapses/73982.html