Study Might Explain Brain Overgrowth Seen in Autism

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 PLoS
Genetics
.

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 billion.

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 RNA
profiles.

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 lifetime.

“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.

More information

The Exploring Origins Project has more on RNA.

Views: 0

You can skip to the end and leave a response. Pinging is currently not allowed.

Leave a Reply

Powered by WordPress | Designed by: Premium WordPress Themes | Thanks to Themes Gallery, Bromoney and Wordpress Themes