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Brain Stem Cells Can Be Awakened, Say Schepens Scientists
Article Date: 07 Jun 2008 - 1:00 PDT
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.
Schepens Eye Research Institute
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Currently, BabelFAmily is financing two promising research projects aimed at finding a cure for Friedreich's Ataxia. Whenever you make a donation to us or purchase a copy of "The legacy of Marie Schlau", this is where all funds raised will be devoted to:
1) Gene Therapy for Friedreich's Ataxia research project:
The project is the result of an initiative of Spanish people affected by this rare disease who are grouped in GENEFA in collaboration with the Spanish Federation of Ataxias and the BabelFAmily. The Friedreich’s Ataxia Research Alliance (FARA), one of the main patients’ associations in the United States now joins the endeavour.
2) Frataxin delivery research project:
The associations of patients and families Babel Family and the Asociación Granadina de la Ataxia de Friedreich (ASOGAF) channel 80,000 euros of their donations (50% from each organisation) into a new 18-month project at the Institute for Research in Biomedicine (IRB Barcelona). The project specifically aims to complete a step necessary in order to move towards a future frataxin replacement therapy for the brain, where the reduction of this protein causes the most damage in patients with Friedreich’s Ataxia.
The study is headed by Ernest Giralt, head of the Peptides and Proteins Lab, who has many years of experience and is a recognised expert in peptide chemistry and new systems of through which to delivery drugs to the brain, such as peptide shuttles—molecules that have the capacity to carry the drug across the barrier that surrounds and protects the brain. Since the lab started its relation with these patients’ associations in 2013*, it has been developing another two projects into Friedrich’s Ataxia.