Brain Stem Cells Can Be Awakened, Say Schepens Scientists

Study Findings Promise to help in treatment of brain diseases

BOSTON, June 6 /PRNewswire/ -- Scientists at Schepens Eye Research
Institute have identified specific molecules in the brain that are
responsible for awakening and putting to sleep brain stem cells, which,
when activated, can transform into neurons (nerve cells) and repair damaged
brain tissue. Their findings are published online this week in the
Proceedings of the National Academy of Science (PNAS).

An earlier paper (published in the May issue of Stem Cells) by the same
scientists laid the foundation for the PNAS study findings by demonstrating
that neural stem cells exist in every part of the brain, but are mostly
kept silent by chemical signals from support cells known as astrocytes.

"The findings from both papers should have a far-reaching impact," says
principal investigator, Dr. Dong Feng Chen, who is an associate scientist
at Schepens Eye Research Institute and an assistant professor of
ophthalmology at Harvard Medical School. Chen believes that tapping the
brain's dormant, but intrinsic, ability to regenerate itself is the best
hope for people suffering from brain-ravaging diseases such as Parkinson's
or Alzheimer's disease or traumatic brain or spinal cord injuries.

Until these studies, which were conducted in the adult brains of mice,
scientists assumed that only two parts of the brain contained neural stem
cells and could turn them on to regenerate brain tissue -- the subgranular
zone (SGZ) of the hippocampus and the subventricular zone (SVZ). The
hippocampus is responsible for learning and memory, while the SVZ is a
brain structure situated throughout the walls of lateral ventricles (part
of the ventricular system in the brain) and are responsible for generating
neurons responsible for smell. So scientists believed that when neurons
died in other areas of the brain, they were lost forever along with their
functions.

In the first study, Chen's team learned that stem cells existed
everywhere in the brain by testing tissue from different parts of adult
mice brains in cultures containing support cells (known as astrocytes) from
the hippocampus, where stem cells do regenerate. In the cultures the stem
cells from other brain regions came to life and turned into neurons.

When they compared the chemical makeup of the areas known to generate
new neurons in the hippocampus with other parts of the brain, the team
discovered that astrocytes in the hippocampus were sending one signal to
the stem cells and that those from the rest of the brain were sending a
different signal to stem cells.

In the second (PNAS) study, the team went on to discover the exact
nature of those different chemical signals. They learned that in the areas
where stem cells were sleeping, astrocytes were producing high levels of
two related molecules -- ephrin-A2 and ephrin-A3. They also found that
removing these molecules (with a genetic tool) activated the sleeping stem
cells.

The team also found that astrocytes in the hippocampus produce not only
much lower levels of ephrin-A2 and ephrin-A3, but also release a protein
named sonic hedgehoc that, when added in culture or injected into the
brain, stimulates neural stem cells to divide and become new neurons.

"These findings identify a key pathway that controls neural stem cell
growth in the adult brain and suggest that it may be possible to reactivate
the dormant regenerative potential by adding sonic hedgehoc, or blocking
ephrin-A2 or ephrin-A3," says Dr. Jianwei Jiao, the first author of the two
papers.

The next step for the team will be to stimulate the sleeping stem cells
in animals who are models of neurodegenerative disorders, such as
Parkinson's disease, to see if the brains can repair themselves and restore
their damaged functions.

Schepens Eye Research Institute is an affiliate of Harvard Medical
School and the largest independent eye research institute in the country.

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[Via Healthcare]