Molecule That Nudges Nerve Stem Cells To Mature Created By UT
Southwestern Researchers
17 Jun 2008 - 2:00 PDT
Inspired by a chance discovery during another experiment, researchers
at UT Southwestern Medical Center have created a small molecule that
stimulates nerve stem cells to begin maturing into nerve cells in
culture.
This finding might someday allow a person's own nerve stem cells to
be grown outside the body, stimulated into maturity, and then re-
implanted as working nerve cells to treat various diseases, the
researchers said.
"This provides a critical starting point for neuro-regenerative
medicine and brain cancer chemotherapy,
assistant professor of molecular biology and senior author of the
paper, which appears online and in the June 17 issue of Nature
Chemical Biology.
The creation of the molecule allowed the researchers to uncover some
of the biochemical steps that happen as nerve cells mature. It also
showed that large-scale screening of compounds can provide starting
points for developing drugs to treat disorders such as Huntington's
disease, traumatic brain injury or cancer.
The scientists began this project as a result of a separate study in
which they were screening 147,000 compounds to see which could
stimulate stem cells cultivated from rodent embryos to become heart
cells. Unexpectedly, five molecules stimulated the cells to transform
into forms resembling nerve cells. The researchers then created a
variation of these molecules, a new compound called Isx-9 (for
isoxazole-9)
relatives because it worked at a much lower concentration and also
dissolved more easily in water.
"It was completely serendipitous that we uncovered this neurogenic
[nerve-creating] small molecule," Dr. Hsieh said. "I think it's one
of the most powerful neurogenic small molecules on the planet. In
theory, this molecule could provoke full maturation, to the point
that the new nerve cells could fire, generating the electrical
signals needed for full functioning.
Nerve stem cells live in scattered groups in various areas of the
brain. They are capable of becoming several different types of cells,
not all of which are nerve cells.
In the study, rodent nerve stem cells from an area of the brain
called the hippocampus were cultured with Isx-9. They clustered
together and developed spiky appendages called neurites, which
typically happens when nerve cells are grown in culture.
Isx-9 also prevented the stem cells from developing into non-nerve
cells and was more potent than other neurogenic substances in
stimulating nerve-cell development. The molecule generated two to
three times more nerve cells than other commonly used compounds.
Neuroscientists believed for decades that the adult mammalian brain
could not grow new nerve cells. Instead, they thought, learning and
memory were strictly a matter of the brain making new connections
between existing cells.
It is now known, however, that the brain constantly creates new nerve
cells. In the hippocampus, which is involved with learning and
memory, stem cells mature into full-blown nerve cells at a rate of
thousands a day, Dr. Hsieh said.
Scientists know that when a mature nerve cell sends a chemical signal
called a neurotransmitter to a stem cell, the immature cell begins to
mature, but they don't know what biochemical pathways or genes are
involved, Dr. Hsieh said.
"The big gap in our knowledge is how to control these stem cells,"
she said.
Isx-9 appeared to act like a neurotransmitter-
nerve stem cells, the researchers found. By culturing the stem cells
with the compound, the scientists identified a possible biochemical
pathway by which stem cells begin to become nerve cells.
The researchers next plan to test Isx-9 on a large number of
different combinations of RNA, the chemical cousin of DNA, to see on
which genes the compound might be working. They have also applied for
a patent on Isx-9 and its relatives.
------------
Article adapted by Medical News Today from original press release.
------------
Other UT Southwestern researchers involved in the study were Dr. Jay
Schneider, assistant professor of internal medicine; Dr. Zhengliang
Gao, postdoctoral researcher in molecular biology; Dr. Shijie Li,
postdoctoral researcher in molecular genetics; Midhat Farooqi, a
student in the Medical Scientist Training Program; Dr. Tie-Shan Tang,
instructor of physiology; Dr. Ilya Bezprozvanny, professor of
physiology; and Dr. Douglas Frantz, assistant professor of
biochemistry.
The work was supported by the Haberecht Wild-Hare Idea Program, the
Donald W. Reynolds Foundation, the National Institute of Neurological
Disorders and Stroke, the Ellison Medical Foundation, the Welch
Foundation and the UT Southwestern President's Research Council.
Dr. Jenny Hsieh
Source: Aline McKenzie
UT Southwestern Medical Center
http://www.medicaln
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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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