Society for Neuroscience – New studies indicate that regular exercise may protect against Parkinson’s disease or reverse some of the devastating consequences of traumatic brain injury. Other studies have found that, contrary to an earlier report, exercising alone appears to be as beneficial as exercising with others, and that the natural mood-enhancing chemical beta-endorphin may be a key player in the ability of exercise to protect the aging brain.
“Everybody knows that exercise is good for your heart, but in recent years we’ve gathered compelling evidence that exercise is also good for your brain,” says Fred Gage, PhD, of the Salk Institute for Biological Studies. “We now know that exercise helps generate new brain cells, even in the aging brain.”
Recent animal studies show that exercise actually helps the regeneration of damaged brain circuits, says Fernando Gómez-Pinilla, PhD, of UCLA.
A major obstacle for the regrowth of severed nerves is overcoming the chemical resistance of cellular substrates. Gómez-Pinilla’s team has found that exercise reduces the inhibitory capacity of the injured brain and thus may help reverse some of the devastating consequences of traumatic brain injury. Such injuries are a major public health problem in the United States, affecting 5 million Americans and costing the country more than $56 billion annually in patient care.
In previous research involving brain-injured rats, Gómez-Pinilla and his colleagues demonstrated that voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF), a protein crucial for the growth of neurons and for brain processes involved in learning and memory. Now they have found that exercise reduces post-trauma increases in the levels of two other proteins, myelin-associated glycoprotein (MAG) and Nogo-A, which inhibit the growth of new axons, the nerve cell fibers that send electrical impulses (messages) to other neurons.
For their recent studies, Gómez-Pinilla’s team subjected rats to an experimental model of traumatic brain injury called fluid percussion injury that reproduces some of the consequences of a strong shake to the head, such as one resulting from a car accident. This injury damaged the hippocampus, an area of the brain involved in memory, learning, and emotion. Some of the injured rats were given access to a running wheel while others remained sedentary. Ten days after the injury, MAG levels rose by 74 percent and Nogo-A levels by 59 percent in the hippocampi of the brain-injured animals compared to a control group of animals given sham injuries. In addition, the injury reduced the levels of protein kinase A (PKA), a brain chemical that enhances the protective effects of BDNF.
Exercise, however, lessened these negatives changes in brain chemistry. MAG levels were 29 percent lower and Nogo-A levels 17 percent lower in brain-injured rats that exercised compared with those that didn’t. Exercise reduced the levels of MAG and Nogo-A in the sham rats (26 percent and 32 percent, respectively) as well. Exercise also increased PKA levels by 33 percent in the brain-injured animals and 22 percent in the shams. In even more recent studies, Gómez-Pinilla’s team has demonstrated that the effect of exercise on reducing axonal growth inhibition is linked to the action of BDNF.
“These findings help us better understand why healing stops after a brain injury,” says Gómez-Pinilla. “More importantly, they show that exercise can counteract the effects of trauma — both by reducing levels of proteins that inhibit new neural growth and by increasing levels of the protein that enhances such growth. This opens the possibility of harnessing this capacity of exercise to promote neural healing.”
A moderate but sustained exercise program also may help slow the progression of Parkinson’s disease or, if started early in life, may prevent the disease from ever developing, suggests new research from Richard Smeyne, PhD, and his colleagues at Saint Jude Children’s Research Hospital in Memphis. About 1 million people in the United States live with this disabling brain disorder, which occurs when cells located in an area of the brain known as the substantia nigra become damaged or destroyed. Symptoms, which tend to worsen over time, include trembling, muscle stiffness, and slowness of movement.
In earlier animal studies, Smeyne and others have shown that very intense levels of aerobic exercise (the equivalent of running a marathon every night) may not only slow the progression of Parkinson’s disease, but may also prevent the brain cells affected by the disease from dying in the first place. Smeyne and his team also found that the levels of cell-destroying neurotoxins in the brain were identical in exercised and sedentary mice – evidence that the exercise must be changing something in the cell itself rather than simply altering the toxin’s metabolism.
In their latest study, Smeyne and his team attempted to determine the minimum amount of exercise needed to protect neurons affected in Parkinson’s disease from becoming destroyed. The mice in the earlier studies had run about 7 kilometers a night (a distance impossible for humans to emulate) for 3 months. In Smeyne’ new study, the animals were allowed to run on exercise wheels for zero, 1, 2, or 3 months and at shorter, predetermined distances — either 1/3 (3,000 revolutions) or 2/3 (6,000 revolutions) of their normal 24-hour running pattern (9,000 revolutions).
“Our findings suggest that at least two months of exercise are needed to protect the cells and that higher levels of exercise were significantly more beneficial than lower amounts, although all exercise was better than none,” says Smeyne. “These findings also suggest that starting an exercise program early in life may be an easy, non-pharmacological way to lower the risk of developing Parkinson’s disease later in life.”
Using 2-dimensional gel electrophoresis, a technique that allows scientists to separate and measure proteins, Smeyne and his colleagues found that three months of sustained exercise significantly altered the expression of numerous proteins in the brain, including ones that help move molecules in and out of cells and that control different gene expression.
New research from Brian Christie, PhD, and his colleagues at the University of British Columbia suggests that, contrary to the findings of a study reported earlier this year, exercising alone has the same positive effect on the brain as exercising with others.
“Over the past several years, research has consistently shown that voluntary exercise can markedly enhance the capacity of the hippocampus to create new neurons,” says Christie. “These new cells in the hippocampus appear to be linked to particular types of learning and memory, and it may be that this region of the brain uses new neurons to help ‘time stamp’ the creation of memories.”
Another research group reported last spring that the benefit of exercise on the creation of new neurons did not occur when animals were socially isolated-unless the animals exercised for a much longer period than their non-isolated peers. To further investigate that finding, Christie and his colleagues assigned mice to either single housing or group housing environments. Some of the animals were quasi-randomly given exercise wheels. After 11 days, the brains of all the animals were examined for signs of enhanced cell proliferation.
“Both individually housed and group housed animals that had access to a running wheel showed significantly more cell proliferation than the animals that didn’t exercise,” says Christie. “In fact, they showed about double the amount of new neurons as the sedentary animals. These findings indicate that voluntary exercise has benefits for the brain in both socially isolated and group housed conditions.”
These findings indicate that exercise can have beneficial effects for the brain, irrespective of whether the activity is performed individually or in groups. Current studies are investigating the possible benefits of exercise for helping ameliorate the structural and functional deficits incurred in the hippocampus in an animal model of fetal alcohol syndrome.
An international team of researchers has found that beta-endorphin, a mood-elevating chemical produced by the hypothalamus and the pituitary gland, may be a key factor in the beneficial effects of exercise on the brain.
“We know that exercise creates new neurons in the hippocampus, a brain region involved in learning and memory. This may explain the increased learning and memory performances observed in people who exercise,” says Muriel Koehl, PhD, of the French National Institute for Health and Medical Research (INSERM) at the University of Bordeaux. “But we have a limited understanding of the underlying mechanisms that cause exercise to create those new cells.”
Suspecting that beta-endorphin may play a role in the stimulatory effect of exercise on the creation of new brain cells (a process known as neurogenesis), Koehl and colleagues at Northwestern University and at the University of Groningen in Haren, the Netherlands, set up an experiment that analyzed the consequences of exercise on different components of neurogenesis (cell proliferation, survival, death, and differentiation) in both adult wild-type (normal) mice and beta-endorphin deficient mice (genetically modified mice that are unable to synthesize beta-endorphin).
The researchers found that in wild-type mice, exercise led to a net induction of adult neurogenesis in the hippocampus by increasing the number (proliferation) of newborn cells and the rate at which those cells survived. No surprise there. What did surprise the researchers were the findings from the beta-endorphin deficient mice.
“In those animals that were sedentary, the lack of beta-endorphin had no effect on neurogenesis,” says Koehl. “In those that exercised, however, we saw that the number of newly born cells was not increased. This strongly suggests a role for beta-endorphin in exercise-induced cell proliferation.”
Interestingly, the researchers also found that the lack of beta-endorphin in exercised animals increased the survival of 1-month-old cells. Altogether, there was thus a net augmentation in the number of newborn neurons in mice lacking beta-endorphin.
“This suggests that different mechanisms may be involved in the exercise-induced increase in cell proliferation and cell survival,” says Koehl. “Our study indicates that beta-endorphin released during exercise may be a key factor in promoting the activity’s proliferative-stimulating effect on the brain, while controlling the total number of new cells created.”
Other work shows evidence that chronic exercise reduces stroke damage in an animal model.
There is burgeoning evidence that exercise provides a neuroprotective benefit in human brain disease, says Michael Davis, PhD, at the University of Texas Health Science Center. However, the mechanisms and biological underpinnings of this phenomenon remain unclear.
Davis’s hypothesis is that long-term exercise promotes new blood vessel growth. This increase in the brain’s capillary bed elevates cerebral blood flow (CBF) which, in turn, serves to help protect against the extensive damage that normally occurs following stroke.
In the unexercised, “couch-potato”, rats the 2-hour stroke produced a 51 percent decrease in CBF. In the exercise group, however, stroke produced only a 16 percent decline in CBF. “This was evidence that exercise provided an approximate 35 percent improvement in brain blood flow subsequent to stroke over that of the control animals,” says Davis.
“The same non-invasive PET imaging tools employed in this project could be applied to evaluate potential stroke-treatments and stroke-prevention strategies in humans,” says Davis. “Our findings support a significant role of exercise in protecting the brain against stroke and perhaps other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s Disease,” he says.
Though these results demonstrate the potential benefit of exercise undertaken before a stroke occurs, adds Davis, no such protection has yet been evidenced for a similar benefit of exercise undertaken after a stroke.