Exercise, The Brain, and a Revolution in Neurology
by Allen Bowling, M.D., Ph.D.
For years, research has shown that exercise has beneficial effects on multiple medical
conditions, including prevention of several forms of cancer and treatment of high blood
pressure, diabetes, and heart disease. Exercise also important role in treating neurological
conditions. In the case of MS, research shows that exercise may improve physical
function, such as strength and walking. It may also aid in the management of multiple
other MS associated conditions, including fatigue, depression, anxiety, osteoporosis, and
bowel and bladder function. The MS related benefits of exercise are so great that if
exercise was a medication, it might be the most common therapy for which I write a
prescription. With years of research in this area, it would seem that the health benefits of
exercise would be quite well understood. In fact, research in the past several years has
identified previously unrecognized aspects of exercise that may dramatically alter our
understanding of exercise and brain function as well as our treatment of neurological
conditions such as MS.
Before considering the direct MS relevance of this recent research, it will be helpful to
provide background information and review the research in other medical conditions.
Growth Factors
A class of very important proteins in the brain and spinal cord is known as nerve growth
factors. Interestingly, much of the early research in this area was done in the mid-1900s
by Dr. Rita Levi-Montalcini, a young Italian-Jewish woman who, during World War II,
was forced to move frequently around Europe and conduct her research under extreme
conditions, including converting her bedroom and a farm house into laboratories and
using sewing needles for surgical instruments.
Ultimately, through courage, determination, and brilliance, she made remarkable
discoveries about nerve growth factors. For these discoveries, she was awarded the Nobel
Prize in 1986. Dr. Levi-Montalcini identified one of the major nerve growth factors—
appropriately, she named it nerve growth factor (NGF). Multiple other growth factors
have subsequently been identified, including a commonly studied protein known as brainderived neurotrophic factor (BDNF).
As their name implies, growth factors stimulate nerve cells to grow. They have several
other characteristics that play a critical role in nervous system function. The major effects
of nerve growth factors are:
• Nerve-regenerating effects
As noted, growth factors stimulate nerves to grow new fibers. In addition, growth factors
strengthen connections between nerves. Through these effects, growth factors, especially
BDNF, may significantly change the structure and function of the nervous system. These
growth factor effects have significantly changed our view of the brain and may be part of
a revolution in neurology. For nearly 150 years, a major concept in neurology has been
that the adult brain operates like a machine. It has been thought that the various nerve
pathways are hardwired” in such a way that one specific area of the brain performs one
specific function. This dogma has now been challenged with research that shows very
clearly that the adult brain can in fact change significantly. For example, the left brain
generally produces movement on the right side of the body. However, many recent
studies demonstrate that, if needed, people may change their brain function in such a way
that they are able to use the right brain to produce movement on the right side of the
body. This amazing adaptation process is known as plasticity. By strengthening nerve
connections and stimulating the growth of new nerve fibers, growth factors play a critical
role in plasticity.
• Nerve-protecting effects
Like any cells in the body, nerve cells can be injured or destroyed by many different
processes, including diseases. A major goal in neurological research is to identify
therapies that can protect nerve cells from injury. Many studies have shown that, through
their growth-promoting effects, nerve growth factors protect nerve cells from various
types of injury.
• Anti-inflammatory effect
In addition to their actions on nerves, growth factors affect the immune system in such a
way that they decrease inflammation. These anti-inflammatory effects may be beneficial
for a variety of medical conditions that are associated with inflammation, including many
aging-related conditions as well as MS and other neurological disorders.
Growth Factors and Exercise
In the past decade, animal as well as human studies have shown that there is a strong
connection between nerve growth factors and exercise. This groundbreaking research,
much of which was conducted by Dr. Fernando Gomez-Pinilla at UCLA, provides a
foundation for improving our understanding of exercise and its effects on the nervous
system. A basic finding in these studies is that exercise stimulates the production of
various growth factors. Through this process, exercise causes brain levels of growth
factors to increase. While it has been known for years that exercise has many health
benefits, these recent findings indicate that exercise may have many therapeutic effects
that we have not yet recognized or used optimally. Specifically, since exercise increases
growth factor levels and growth factors have such diverse and potentially beneficial
effects on the brain, it is possible that, when used appropriately, exercise may provide a
valuable strategy for preventing or treating a variety of neurological and psychiatric
conditions.
Neurological Diseases and Depression
Exercise and nerve growth factor research has been conducted on a variety of medical
conditions. To date, much of this disease-related research has focused on conditions other
than MS. In animal models of trauma to the brain or spinal cord, it has been shown that
exercise appears to provide beneficial effects through its stimulation of growth factors,
especially BDNF. While one generally thinks of physical exercise improving physical
function, such as strength or walking, these studies in trauma have shown that physical
exercise may also improve non-physical function, such as sensation or thinking
processes. This somewhat paradoxical effect may be due to the fact that exercise
increases BDNF levels generally in the nervous system—BDNF is then able to produce
its effects on multiple types of nerves.
Growth factor research has also been done in various aging-related neurological
conditions, such as Parkinson’s disease, Alzheimer’s disease, and Lou Gehrig’s disease
(amyotrophic lateral sclerosis or ALS). Exercise decreases the severity of disease in the
animal models of Parkinson’s disease, Lou Gehrig’s disease, and Huntington’s disease. In
addition, exercise may decrease the risk of developing Parkinson’s disease. Interestingly,
one of the best therapies for the animal model of Lou Gehrig’s disease is to increase
growth factor levels with a drug-based approach in combination with a regular exercise
program—this unique strategy uses exercise to increase the beneficial effects of a drugbased approach. Recent growth factor research has also led to valuable insight into the
effects of exercise on depression. Over the past few decades, there have been more than
1,000 studies of exercise and depression—most of these have shown that depression is
decreased by a regular exercise program. How this occurs has been a mystery. In late
2007, a research study reported that exercise-related anti-depressant effects may be due to
an increase in the levels of a specific growth factor, VGF. In animal studies, inhibition of
VGF is associated with depression, while treatment with VGF produces anti-depressant
effects. This research, which originated through exercise studies, may eventually lead to
the development of new antidepressants that produce their effects through VGF.
Is Exercise Just About Growth Factors?
When research leads to the identification of an underlying mechanism for a complex
process such as exercise, it is tempting to explain everything in terms of that newly
identified mechanism. Specifically, in the case of the recent exercise research, it is
tempting, but naïve and simplistic, to assume that all of the nervous system benefits of
exercise can be explained by increased growth factor levels. In fact, the benefits of
exercise are probably due to growth factors working in combination with other processes,
one of the most important of which may be the exercise induced activation of multiple
nerve pathways in the brain. Activation of these pathways, along with the biological
effects of growth factors (as well as other processes), may produce the neurological
benefits of exercise, especially plasticity.
What About MS?
As noted, much of the research on growth factors and exercise has not been done
specifically in MS. There certainly is strong theoretical support for growth factors
playing an important role in the treatment of MS. The various actions of growth factors
may provide valuable treatment possibilities:
• Nerve-regeneratinge effects: may improve nerve function after injury and, if needed,
facilitate the development of new pathways.
• Nerve-protecting effects: may prevent nerve injury by making nerves less vulnerable to
the disease process of MS.
• Anti-inflammatory effects: may also prevent nerve injury by decreasing immune-system
attack on the nervous system.
In the limited studies of MS and growth factors that have been done thus far, one specific
nerve growth factor, known as IGF-1 (insulin-like growth factor-1), has been shown to be
an effective therapy for the animal model of MS. In another study of people with MS, 30
minutes of exercise was shown to increase the Rocky Mountain MS Center blood levels
of BDNF. Although the studies of growth factors and exercise in MS are limited, this
area of investigation offers much hope and provides clear directions for future research.
The results of research in other conditions should provide motivation for people with MS
who are pursuing, or in the process of developing, an exercise regimen. It is important to
keep in mind that exercise is readily available (no prescription is required!), generally
safe, and usually inexpensive.
As a result, within reasonable limits, people with MS may do some of their own research
to determine the forms of exercise that are most helpful for them and to identify the
expected, as well as unexpected, benefits of a regular exercise program.
Spring 2008
Taken from InforMS
Volume 24, Issue 2
Rocky Mountain
Multiple Sclerosis Center
http://www.mscenter.org/content/view/14/228/