Extra Brain Synapses Appear a Hallmark of Autism A surplus of synapses pack the brains of children and adolescents with autism—an excess due to a slowdown in normal “pruning” during development, according to a study published online Aug. 21 in Neuron. Because synapses are the points where neurons connect and communicate with one another, the excessive synapses may ... Research in Brief
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Research in Brief  |   November 01, 2014
Extra Brain Synapses Appear a Hallmark of Autism
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Special Populations / Autism Spectrum / Research in Brief
Research in Brief   |   November 01, 2014
Extra Brain Synapses Appear a Hallmark of Autism
The ASHA Leader, November 2014, Vol. 19, online only. doi:10.1044/leader.RIB3.19112014.np
The ASHA Leader, November 2014, Vol. 19, online only. doi:10.1044/leader.RIB3.19112014.np
A surplus of synapses pack the brains of children and adolescents with autism—an excess due to a slowdown in normal “pruning” during development, according to a study published online Aug. 21 in Neuron.
Because synapses are the points where neurons connect and communicate with one another, the excessive synapses may profoundly affect how the brain functions. Neuroscientists at Columbia University Medical Center found that a drug that restores normal synaptic pruning can improve autistic-like behaviors in mice, even when the drug is given after the behaviors have appeared.
Although the drug, rapamycin, has side effects that may preclude 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,” says senior investigator David Sulzer, a professor of neurobiology in the CUMC departments of psychiatry, neurology and pharmacology.
A burst of synapse formation occurs in normal brain development in infancy, particularly in the cortex, a region involved in autistic behaviors; pruning eliminates about half of these cortical synapses by late adolescence. 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.
To test this hypothesis, co-author Guomei Tang, CUMC assistant professor of neurology, examined brains from children with autism who had died from other causes. Thirteen brains came from children ages 2 to 9, and 13 brains came from children 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 and found that by late childhood, spine density had dropped by about half in the control brains, but by only 16 percent in the brains from 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 says, “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 study also revealed clues about what caused the pruning defect; the brain cells of children with autism were filled with old and damaged parts and were deficient in a degradation pathway known as autophagy, which cells use to degrade their own components.
Using mouse models of autism, 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. “While people usually think of learning as requiring formation of new synapses,” Sulzer says, “the removal of inappropriate synapses may be just as important.”
“What’s remarkable about the findings,” said 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.”
1 Comment
November 20, 2014
critical periods
Critical or sensitive periods of neural development permit the environment to exert enhanced effects upon the nervous system. But lots can go wrong with these periods (poorly timed, too mild, too exuberant, etc.) One unfortunate possibility is that a period may open and fail to close. The latter seems consistent with what this research found with mTOR.
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November 2014
Volume 19, Issue 11