Researchers Link Early Stem Cell Mutation To Autism
ScienceDaily (July 1, 2008) — In a breakthrough scientific study
published June 30 in the Proceedings of the National Academy of
Sciences, scientists at the Burnham Institute for Medical Research
have shown that neural stem cell development may be linked to Autism.
The study demonstrated that mice lacking the myocyte enhancer factor
2C (MEF2C) protein in neural stem cells had smaller brains, fewer
nerve cells and showed behaviors similar to those seen in humans with
a form of autism known as Rett Syndrome.
This work represents the first direct link between a developmental
disorder of neural stem cells and the subsequent onset of autism.
The research team was led by Stuart A. Lipton, M.D., Ph.D., a
clinical neurologist and Professor and Director of the Del E. Webb
Neuroscience, Aging and Stem Cell Research Center at Burnham.
"These results give us a good hint of how to look at Rett Syndrome
and potentially other forms of autism in humans," said Dr.
Lipton. "Having identified a mutation that causes this defect, we can
track what happens. Perhaps we can correct it in a mouse, and if so,
eventually correct it in humans."
Discovered in Dr. Lipton's laboratory, MEF2C turns on specific genes
which drive stem cells to become nerve cells. When MEF2C was deleted
from neural stem cells in mice, there was a faulty distribution of
neurons accompanied by severe developmental problems. Adult mice
lacking MEF2C in their brains displayed abnormal anxiety-like
behaviors, decreased cognitive function and marked paw clasping, a
behavior which may be analogous to hand wringing, a notable feature
in humans with Rett syndrome.
"There's a yin and yang to this MEF2C protein," said Dr. Lipton. "My
laboratory recently showed that MEF2C induces embryonic stem cells to
become neurons. In this new research, we show that knocking out MEFC2
in the brain results in mice with smaller brains, fewer neurons and
reduced neuronal activity. The commonality is the protein's
association in making new neurons."
Collaborators were Drs. Hao Li, Shu-ichi Okamoto, Nobuki Nakanishi
and Scott McKercher, of Burnham, as well as Dr. Amanda Roberts from
The Scripps Research Institute and Dr. John Schwarz from the Albany
Medical Center.
Rett syndrome, a form of autism, afflicts more girls than boys and
results in poor brain development, repetitive hand motions, altered
anxiety behaviors and the inability to speak. Patients with Rett
Syndrome also suffer from seizures and other debilitating
neurological symptoms.
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Adapted from materials provided by Burnham Institute, via
EurekAlert!, a service of AAAS.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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