Running Boosts Brain Cell Numbers In Neurodegenerative Disease Model

"The results suggest that exercise might delay the onset and progression of some neurodegenerative diseases," said Carrolee Barlow, a Salk assistant professor and lead author of the study, published in the current issue of Genes and Development.

It also appears that the miles logged correlate directly with the numbers of increased cells. In the study, the Salk team monitored the number of revolutions each mouse lapped on a running wheel placed in its cage.

"It's almost as if they were wearing pedometers," said Barlow. "And those that ran more grew more cells."

The mice in the study were missing a gene, Atm, known to be mutated in the disorder Ataxia-telangiectasia, commonly referred to as A-T. Caused by the death of brain cells, A-T is characterized by a progressive loss of motor control that typically confines patients to wheelchairs by adolescence. The cell death appears first in the cerebellum, the brain region directing movement, but occurs throughout the brain. "A-T is rare," said Barlow, "but at the cellular level it shares properties with more common diseases such as Alzheimer's. For example, we know that brain cells in both conditions are highly susceptible to oxidative stress, damage from what are commonly called free radicals."

She added that the current study demonstrated running's brain-boosting effects in the hippocampus, a region of the brain linked to learning and memory and known to be affected by Alzheimer's disease.

"Therefore, what we can learn from the A-T model mouse may very well be relevant to other neurodegenerative conditions," said Barlow.

In the study, both normal and A-T mice were given running wheels to use for several weeks, at the end of which their brains were monitored for new cells and compared to non-running counterparts. The investigators found that running didn't increase the number of new brain cells in the A-T mice; however, the exercise did have a significant impact on cell survival.

"In sedentary A-T mice," said Barlow, "it appears that most newly born brain cells die. We don't understand that fully, but it probably has something to do with an inability to cope with oxidative stress.

"Running appears to 'rescue' many of these cells that would otherwise die. It suggests that staying active may help delay progression of neurodegenerative conditions."

Barlow added that the experiments were carried out in young mice, since A-T mice, like their human counterparts, experience mobility loss as they age.

"What we need to do now is figure out what exercise is doing to help these brain cells survive," said Barlow. "It must be altering brain chemistry - altering levels of particular hormones or growth factors, perhaps. If we can identify the specific molecules responsible for running's effects, those molecules should point to new drug strategies to treat A-T and other neurodegenerative diseases."

The current study builds on work directed by Salk Professor and co-author Fred Gage, showing that running leads to increased brain cell numbers in normal adult mice, elderly "senior citizen" mice and a genetically "slow-learning" strain of mice. Gage's studies showing that new cell growth occurs also in human brains suggests the boosting effects of running may occur in people as well.

Additional Salk co-authors include Duane Allen, Henriette van Praag, Jasodhara Ray, Christopher Winrow, and Todd Carter. The study was done in collaboration with Zoe Weaver and Thomas Reid at the National Institutes of Health; Ray Braquet and Kevin Brown at Louisiana State University; and Elizabeth Harrington at Massachusetts General Hospital. The study, titled "Ataxia telangiectasia mutated is essential during adult neurogenesis," was supported by the National Institutes of Health, the A-T Children's Project, the Lookout Fund and the Searle Family Trust. Barlow holds the Frederick B. Rentschler Developmental Chair at The Salk Institute.

The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit institution dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. The Institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.