Feb. 17, 2004 – Studies showing that elderly “senior
mice,” as well as their younger brethren can increase their brain
cells by running has found new support in study by scientists at The
Salk Institute.
They found
additional evidence that running can boost brain cell survival in
animals with neurodegenerative disease.
"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 at 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.
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