Public Release: 

Exercise has a more powerful impact on the brain than previously thought

May lead to improved treatments for disorders such as spinal cord injury

Society for Neuroscience

Scientists are learning that exercise has a much more direct and powerful impact on the brain than previously believed -- an exciting discovery that may lead to safer and more effective approaches to preventing and treating a variety of brain injuries and diseases, from spinal cord injuries to depression.

"A growing number of studies are demonstrating that some form of regular exercise -- or even the mental practice of exercise -- can have beneficial effects on a wide variety of daily functions," says V. Reggie Edgerton, PhD, of the University of California at Los Angeles. "For example, mental practice can improve one's strength, and regular exercise, both before and after a spinal cord injury, will reduce the severity of the injury." Research is also showing that regular exercise seems to have a generalized beneficial effect in how the brain functions, as shown by its ability to reduce symptoms of depression in both animals and humans.

"Just how exercise is modulated in these important functions is not clear," says Edgerton, "but new experiments showing enhanced vascularity in areas of the brain associated with motor control in nonhuman primates provides an example of a change in the tissues of the brain." These results may have important implications for helping people recover from vascular injuries and trauma.

In general, all of this latest research on exercise and the brain seems to suggest that some minimum level of physical activity is important for keeping the brain functioning at normal levels. "Exercise affects more than the muscle," says Edgerton.

At the Cleveland Clinic Foundation, researchers have found that older people must put some mental effort into exercising if they want their muscles to become stronger. "We found that low-intensity physical exercise does not alone produce sizable strength gains in healthy elderly individuals," says Guang Yue, PhD. "To achieve significant muscle strength, you also need to put a high level of mental effort into your exercise routine." Last year, Yue's team reported similar findings among young adults.

To investigate the effect of different levels of mental effort on improving muscle strength in the elderly, Yue's study enlisted 36 healthy volunteers aged 65 to 93. One group was instructed to mentally "urge" their muscles to contract strongly while doing low-intensity (30 percent of maximum level) exercises to strengthen their elbow flexor muscles. Others performed the same exercises with low mental effort--while watching television.

Yue and his colleagues found that the muscles of the group that performed the exercises with low mental effort showed only a small improvement in strength -- about 3 percent. The muscles of the group that trained with high mental effort, on the other hand, grew significantly stronger -- by about 15 percent. The brain signal, measured by scalp EEG-derived movement-related cortical potential, also increased in the high mental effort group, but not in the low mental effort group. "This suggests that the strength gains from the high mental effort training resulted primarily from an enhanced brain signal to muscle," says Yue.

The study's findings may change current methods of rehabilitation therapy for patients of all ages who are able to perform only low- to moderate-intensity exercise after an illness or injury. "It's well known that people recuperating from neuromuscular injuries or diseases have a long road to recovery," says Yue. "Our research suggests that recovery could be accelerated by combining low- or moderate-intensity physical therapy with mental practice."

Yue's team will next evaluate the effects of mental training in the frail elderly, who have difficulty performing traditional strength training, and in patients recovering from certain neuromuscular disorders, such as stroke. In addition, they will attempt to determine the neural mechanisms that mediate mental training-induced strength improvements -- which areas of the brain are trained, for example, and what types of changes occur in each area.

Recent animal studies from the University of California-Irvine (UCI) have found that exercise done both before and after a spinal cord injury can significantly improve recovery of locomotor function. These findings may lead to more effective treatments for the 11,000 people who sustain new spinal cord injuries every year in the United States. Up to 400,000 Americans are currently living with a spinal cord injury, according to the National Spinal Cord Injury Association.

To study the effect of exercise on the recovery from spinal cord injuries, Carl W. Cotman, PhD, and his colleagues at UCI used two groups of 10 mice. One group was housed in individual cages with flat-surfaced running wheels, in which they could run voluntarily; the mice in the other group were put in cages without running wheels. The physical activity of the animals with the running wheels was carefully recorded. After three weeks, all the mice underwent surgery to receive a moderate spinal cord injury, then they were returned to their cages. During the next eight weeks, as the mice recovered from their injuries, their locomotor abilities were observed.

"The running mice reached a higher level of walking compared to the sedentary mice," says Cotman. "The running mice were able to take frequent to consistent steps and showed occasional to frequent coordination. The sedentary animals, on the other hand, took only occasional steps and didn't achieve any level of coordination in walking."

The size of the spinal cord injury was not different between the two groups, Cotman stresses. "This suggests that the running may have changed cellular function in a part of the spinal cord that was not injured -- perhaps in the motor neurons of the muscles of the animals' hind limbs," he says.

Cotman and his colleagues plan to next determine whether voluntary exercise done after but not before a spinal cord injury will also improve recovery. Initial results suggest that it does. "In addition, we've found that mice that run three days each week are recovering just as well as those that run seven days a week," says Cotman. "This suggests that physical therapy may not be needed every day to be beneficial."

Other studies by Cotman and his team suggest that exercise may help protect the elderly from depression -- not only by increasing blood flow to the brain, but by directly affecting the cells of the nervous system. "Voluntary exercise was previously thought to benefit only the periphery system -- heart, muscles, bones and so on," says Cotman. "We're finding, however, that it directly affects the central nervous system."

These results indicate that exercise may have an important -- perhaps a crucial -- role to play in the prevention and treatment of depression, particularly in later life.

Using animal models, the UCI researchers studied the effect of voluntary physical exercise on the induction of a particular brain chemical, a protein called brain-derived neurotrophic factor (BDNF) in an area of the brain, the hippocampus, that is involved in learning and memory. BDNF is known to have antidepressant-like properties, and has been found in lower levels in the blood of people with major depression.

Cotman and his colleagues measured the induction of BDNF in the brains of young (2 month), late-middle-aged, (15 month) and old (24 month) rats before and after various periods of exercise. "We found that the induction of BDNF in each age group rose significantly after one week of exercise," says Cotman. When all the groups were tested with a task that is used to assess levels of depression, the old animals showed significant improvement. In fact, they performed as good as or even better at the task than the youngest animals.

"This is an exciting result," says Cotman. "Translated into human terms, it means that individuals who are appropriately physically active may be able to protect themselves from depression -- or be less depressed or relieved from depression -- if they are physically active." He and his colleagues next plan to determine how much physical activity and how often the activity needs to be done to have an effect on depression.

Researchers at the University of Texas Southwestern Medical Center at Dallas have also been studying the effect of exercise on depression. In a pilot clinical trial, they have found that adding exercise to antidepressant medications significantly reduces depressive symptoms in patients with major depressive disorders.

The study involved 17 patients with major depression. All were taking a single antidepressant medication, but were still experiencing residual symptoms of depression, such as insomnia, lack of concentration, irritability, sleep problems, lack of motivation, and sadness. "Many patients often continue to have symptoms even when they have been effectively treated with an antidepressant medication," explains Madhukar Trivedi, MD. "Not only do these residual symptoms have adverse effects on the patient's quality of life, they also increase the likelihood of a new full-blown depressive episode."

Participants in the study were prescribed a 12-week aerobic exercise program (walking, treadmill, or cycling) based on the U.S. Surgeon General's recommendations (at least 30 minutes of moderate physical exercise on most days of the week). Each week the severity of the patients' depressive symptoms were evaluated using both clinician- and patient-rated instruments. "We found that exercise had a marked effect on reducing symptoms," says Trivedi. "These findings suggest that prescribing exercise along with antidepressant medications could prove to be an effective strategy for the treatment of major depression." Trivedi and his colleagues at are now recruiting patients for a larger, controlled clinical trial.

A recent study from William Greenough, PhD, and Im Joo Rhyu, PhD, of the University of Illinois and Judy Cameron, PhD, of the University of Pittsburgh has demonstrated that regular aerobic exercise increases the number of capillaries in the motor cortex, a small area on the outer part of the brain that controls voluntary muscle movements. This study, which involved mature adult macaque monkeys, is the first to demonstrate that exercise has an effect on capillaries in a primate brain.

"Our research indicates that physical exercise is good for the brain not just because of its effect on peripheral tissues, such as the heart and major body arteries, but also because of its direct effects on brain vasculature," says Rhyu. The research also suggests that brain plasticity -- the ability of the brain to reorganize itself in response to sensory stimulation -- may not be restricted to nerve cells and their synapses. Other elements of brain tissue, including its capillaries, may be involved as well. Understanding how brain plasticity works is essential to developing interventions to reduce effects of aging and overcome brain damage caused by injury or disease.

For the study, 3 mature adult female macaque monkeys were trained to run on modified motorized treadmills for one hour a day (about 2 miles per day), five days a week for 20 weeks. The monkeys ranged in age from 15 to 18 years, which meant they were at least halfway through their lifespan. Macaque monkeys, which are physiologically very similar to humans, reach adulthood at about 4 years of age and generally live to be 22 to 30 years old.

After the 20 weeks, the animals' brain tissue was examined using an antibody to CD 31, a marker of the endothelial cells that line capillaries. This antibody is commonly used by oncologists in studies of cancer. The volume of brain tissue occupied by capillaries in the exercising monkeys was shown to have increased relative to values in 3 unexercised controls. "The greatest increase was in the layers of the cortex containing the large neurons that project to the spinal cord, and those neurons initiate and guide muscular activity," says Rhyu.

Next, Rhyu plans to explore whether exercise has a similar effect on other regions of the brain. "We'd especially like to know whether the blood supply to regions of the brain involved in cognitive performance is altered by exercise," he says. Such a finding could help explain why previous studies in both humans and animals have shown that physical exercise, particularly aerobic exercise, can improve performance on a variety of cognitive and skilled performance tasks.

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