Children With Autism Have Extra Synapses In Their Brains
Autism Spectrum Disorder (ASD) affects about 1 in 68 children born in the United States. In an effort to find out why, a group of researchers led by David Sulzer at Columbia University Medical Center examined the synapses in the brains of children with autism. They discovered that during childhood, children with autism do not undergo regular synaptic pruning, resulting in having an excess. This also identified a potential conversion of genetic targets that could be used to create a new treatment for ASD. The paper was published in the journal Neuron.
Throughout childhood development, regular cellular processes get rid of about half of the synapses the child was born with. Synapses allow neurons to communicate with one another through chemical or electrical signaling. Though some have speculated that excess synapses could be a sign of autism, there had not been any studies on the matter until now.
Sulzer obtained brains from about two dozen children with autism from ages 2-20 who had died from unrelated causes. Those brains were compared with about two dozen brains from developmentally typical children as a control. While looking at the neurons, the children with autism had more synaptic “spines” than the control group. Many of these synapses were damaged and had not been cleared out by autophagy, which is the body’s way of cleaning out imperfect structures.
“It’s the first time that anyone has looked for, and seen, a lack of pruning during development of children with autism,” Sulzer explained in a press release, “although lower numbers of synapses in some brain areas have been detected in brains from older patients and in mice with autistic-like behaviors.”
Autophagy is regulated by a protein called mTOR. Children with autism have overactive mTOR, which prevents autophagy from ‘cleaning house’ and getting rid of the damaged synapses. Sulzer’s team replicated the condition in mice, and then gave them a drug that suppressed mTOR. They were able to balance mTOR function and prune off some of those extra damaged synaptic connections, resulting in a reduction of ASD-associated behavior. Unfortunately, the drug isn’t ideal for potential use in humans anytime soon. It is, however, an encouraging start.
“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,” Sulzer said.
While the discovery of these extra synapses is incredible, the fact that the mTOR pathway converges on many known genetic causes of ASD could be the key to creating a reliable treatment for many of these disorders.
“What’s remarkable about the findings,” continued Sulzer, “is that hundreds of genes have been linked to autism, but almost all of our human subjects had overactive mTOR and decreased autophagy, and all appear to have a lack of normal synaptic pruning. This says that many, perhaps the majority, of genes may converge onto this mTOR/autophagy pathway, the same way that many tributaries all lead into the Mississippi River. Overactive mTOR and reduced autophagy, by blocking normal synaptic pruning that may underlie learning appropriate behavior, may be a unifying feature of autism.”
Read more: http://www.iflscience.com/brain/children-autism-have-extra-synapses-their-brains
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