Interesting article off of ScienceDaily. And another from a Stem Cell Center press release.

Awakening Brain Stem Cells
09 Jun 2008

MA-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 brain¹s 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 is responsible for generating neurons reponsible 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 hedghoc 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.


A researcher in California is working with human stem cells, the article in part . . .

UCR Researcher Awarded $2.1 Million Stem Cell Grant to Study Alzheimer’s Disease

Douglas Ethell will use human embryonic stem cells to develop a method for stimulating protective immune responses that could reduce or prevent cognitive loss in Alzheimer's patients.

RIVERSIDE, Calif. – UC Riverside’s Douglas Ethell, an assistant professor of biomedical sciences who studies how brain cells die in disorders such as Alzheimer’s and Parkinson’s, has been awarded a $2,120,833, five-year grant by the California Institute for Regenerative Medicine (CIRM), California’s stem cell research initiative.

The grant, called a New Faculty Award by CIRM, will fund Ethell’s research on human embryonic stem cells for treating Alzheimer’s disease, the most common cause of dementia in the elderly.

Approved yesterday by the Independent Citizens Oversight Committee (ICOC), the governing board of CIRM, the grant is designed to encourage and foster the next generation of clinical and scientific leaders in stem cell research.

“Stem cell technology is the future of medicine, and CIRM is ensuring that California continues to play a leading role in developing this important technology,” Ethell said. “This new investigator grant is a tremendous boost to my research as it will allow me to recruit talented students, postdoctoral researchers and technicians to work on stem cells in my lab. Moreover, the comprehensive nature of CIRM’s funding commitment will allow me to spend less time writing grants and more time doing research.”

Alzheimer’s disease affects more than five million people in the United States. It has been estimated that the number of Alzheimer’s disease patients in the country will grow to 13 million by 2050. Currently, there is no effective treatment or cure for the disease.

“In recent years it has become clear that the immune system can protect and maybe even reverse some of the effects of Alzheimer’s disease,” Ethell said. “Our research has shown that Alzheimer’s responsive T cells can have beneficial effects in mouse models of the disease. This grant will allow us to take this project to the next level by using immune cells and neurons derived from human stem cells.”

Ethell’s proposed research will involve the use of human embryonic stem cells – cells that can become any kind of cell in the body – to develop a method that would stimulate the production of “beta-amyloid responsive T cells.” These T cells coordinate immune responses that reduce brain levels of a toxic Alzheimer’s-related molecule, called beta-amyloid peptide, thereby improving memory.

Specifically, Ethell’s lab will stimulate the embryonic stem cells to become a certain kind of immune cell, called a dendritic cell. By engineering the stem cells to express certain proteins, his lab will attempt to coax the dendritic cells into activating Alzheimer’s specific immune responses.

“This approach will allow us to determine the best strategies for turning on beneficial Alzheimer’s immune responses in human patients,” Ethell said. “An eventual therapeutic strategy for the disease may be isolating different kinds of stem cells from a patient to make dendritic cells that can then be given back to the same patient, which would turn the beneficial responses back on. Such a therapeutic approach could greatly reduce cognitive decline in Alzheimer’s disease and alleviate some of the enormous emotional, social and financial burden caused by this disease.”

The UCR website: http://www.stemcell.ucr.edu/

The full news release can be found here: http://www.newsroom.ucr.edu/cgi-bin/display.cgi?id=1733

Very, very interesting. Thanks, Leela.