FRIDAY, March 23 (HealthDay News) -- Researchers report that
they have identified abnormalities in the DNA and RNA of cells in
the prefrontal cortex of the brains of autistic children.
The findings may help to explain the underlying mechanism for
the brain "overgrowth" that prior reports have documented in
autistic children. Those studies have found that the brains of
young children with autism are larger than the brains of
non-autistic children, particularly in the prefrontal cortex. The
prefrontal cortex is key to complex thoughts and behaviors,
including language, social behavior and decision-making.
This growth abnormality likely contributes significantly to the
social, communication, and emotional deficits common among people
with autism, the researchers said.
In the new study, researchers analyzed tissue from the
prefrontal cortexes of 33 postmortem brain samples from autistic
and non-autistic people aged 2 to 56.
In addition to DNA differences known as copy number variations,
researchers also did genome-wide RNA profiling and found
differences in RNA between the autistic and non-autistic brains.
RNA (ribonucleic acid) plays crucial roles within cells, serving as
an intermediary between DNA, the blueprints for genetic
information, and the production of proteins that carry out a vast
array of vital activities in cells.
The RNA abnormalities appear to be involved with genes that code
for proteins regulating cellular growth, the researchers said.
"What we found was the networks that are supposed to regulate the genesis of brain cells and develop them were abnormal. The networks that were supposed to regulate DNA repair were turned down. And the networks supposed to regulate neuron removal and survival were abnormal," said study author Eric Courchesne, director of the Autism Center of Excellence at the University of California, San Diego (UCSD) School of Medicine.
The study is published in the March 22 issue of
How might these differences fit into the autistic picture?
Preliminary research by the UCSD team found that an excessive
amount of neurons, or brain cells, might account for the
overgrowth. While typically developing kids had about 0.88 billion
neurons in the prefrontal cortex, autistic children had about 1.57
According to the researchers, the copy number variations along
with the RNA abnormalities may disrupt the cell cycle and may
explain the underlying mechanism driving the overgrowth.
"We found DNA defects, or copy number variations, in a variety of genes that regulate cell production and cell survival," Courchesne said. "To us, that suggests the explanation for why there are an abnormal number of neurons in the prefrontal cortex. Those genes fall into networks that control the number of neurons generated and the number that survive in prenatal life."
Researchers also noted that the RNA differences vary, depending
on the age of the brain, with children and adults having different
Courchesne said that the way the brain responds to that
overgrowth of neurons -- in other words, what's happening in those
repair pathways -- may help to explain why people with autism may
have different trajectories, with some seeming to regress and
others continuing to learn new skills throughout their
"In adulthood, we see individuals that continue to improve, and continue to gain more and more skills and abilities," Courchesne said. "Then there are others that don't show that continued, ongoing improvement or show the opposite. My best guess is the trajectory has less to do with the original cause of the autism, than with an individual's specific composition of genes, or the available genes to remodel the brain."
Robert Ring, vice president for translational research at Autism
Speaks, said researchers offer up a provocative and plausible
theory. However, he noted that while brain overgrowth is
well-established, only one, small study has shown that the
explanation for it is too many neurons.
"What's valuable about the approach this group has taken is that they've gone directly to the tissue of interest, and have asked, 'Is there any evidence there are abnormalities in the expression of genes that correlate with the neuro-anatomic or cellular findings that have been reported?'" Ring said.
"What they're reporting is there is indeed some evidence that particular pathways might be disregulated in the autistic brain vs. the control brain, and some of these pathways, when you look at their function, may be a plausible explanation for the increased growth and increased cell number."
The study, Ring added, offers up new clues for researchers to
pursue, but nothing is proven. "There is an enormous amount of work
needed to confirm this," he said.
Exploring Origins Project has more on RNA.
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