Does exercise impact Parkinson’s?
We all know that exercise is essential to good health. It is good for the heart and the muscles, but did you know that exercise can actually change the brain and have a positive impact on Parkinson’s symptoms? Research from the Parkinson's Outcomes Project, the largest-ever clinical study of Parkinson’s, found that people with PD who engaged in at least 2.5 hours of exercise a week had a better quality of life than those who didn't exercise at all or started exercising later. Establishing early exercise habits is an essential part of overall disease management, which is why neurologists now recommend exercise as part of most PD treatment plans.
Current Exercise Research
At Rhodes University in Memphis, TN, Dr. Gerecke and team report that exercise can protect mice against toxic exposure. MPTP is a neurotoxin that is used as an animal model for Parkinson’s disease (PD), as it selectively kills A chemical messenger (neurotransmitter) that regulates movement and emotions. neurons in the substantia nigra, the same area of the brain that degenerates in PD. Dr. Gerecke showed that three months of exercise provided complete protection against MPTP-induced neurotoxicity in mice. If running was limited to one to two months, or if the amount of running daily was decreased, the protective effects of exercise were abolished. Thus, daily, sustained exercise was necessary for full protection.
Gerecke also performed proteomic analysis to identify possible mechanisms of this protection, and found three months of exercise induces changes in proteins related to energy regulation, cellular metabolism, cytoskeleton dynamics and intracellular signaling events.
At the University of Pittsburgh, Dr. Zigmond et al. found that exercise reduces the impairments elicited by the dopaminergic neurotoxins as well as the loss of DA neurons. This study is focused on one possible explanation for the beneficial effects of exercise: an exercise-induced increase in the expression of neurotrophic factors, particularly GDNF (glial-derived neurotrophic factors).
Researchers observed that GDNF can reduce the vulnerability of DA neurons, in part due to the activation of key intracellular cascades. This raises the possibility that some people with PD have less of these neuroprotective mechanisms, so treatments boosting them — including exercise — may provide therapeutic benefit.
- Out of 14 studies on treadmill training, three show an immediate effect of increased walking speed, longer stride length and improved balance as early as after one treadmill session. Eleven longer-term trials demonstrated safety and positive benefits in gait speed, strike length and related quality of life even several weeks later.
- At the Cleveland Clinic, Dr. Alberts et al. found that when people with PD pedaled on a stationary bike 30 percent faster than their preferred “voluntary” rate, they gained in aerobic fitness and showed improvement in motor function and coordination as well as manual dexterity. This improvement was retained for weeks after exercise stopped.
- In a recent study conducted by Beth Fisher et al., researchers at the University of Southern California found exercise may impact the brain. On a day-to-day basis, people with PD who exercised moved more normally than those who did not. Based on these findings, they believe exercise may help the brain to maintain old connections, form new ones and restore lost ones. They suggest that, in certain situations, the neuroplasticity created from exercise in people with PD may actually outweigh the effects of neurodegeneration.
The above are just some of the mounting evidence that shows that for people with PD, exercise is an essential part of managing the disease. Researchers are working to better understand this and how to achieve the best results. The Parkinson’s Foundation supports their efforts.
Can the brain change?
We know that in PD, neurons (brain cells) that produce the chemical transmitter dopamine are damaged and lost. We also know that there is a pause between the time when the loss of neurons begins and the time when PD motor symptoms start to show. By the time most people are diagnosed, nearly 80 percent of their dopamine neurons are already gone.
During this pause, the brain is changing, compensating for the loss of dopamine neurons occurs during the process of neurodegeneration. The brain reshapes itself throughout life in response to experience. As children learn motor skills, their brain cells make connections and this process continues through adulthood.
Scientists call this ability to change and compensate exercise-dependent neuroplasticity. Exercise may affect the brain by driving this compensation. On a daily basis, people with PD who exercise can move more normally than those who do not. We believe that exercise may be contributing to neuroplasticity — helping the brain maintain old connections, form new ones and restore lost ones. This may outweigh the effects of neurodegeneration.
But what has been proven? There is compelling scientific evidence in animal models of PD that intensive exercise can alter the way the brain works and promote recovery. Research at the University of Southern California (USC) shows how exercise improves walking and other motor skills in people with PD. It is also shedding light on how exercise influences neuroplasticity at the molecular level.
Exercise for Improved Walking and Balance in PD
Scientists who study stroke and traumatic brain injury have identified four features of exercise that drive neuroplasticity: intensity, specificity, difficulty and complexity.
To explore whether these findings apply to PD, there are investigations into the effect of exercise in two ways. One study was in mice that had been made Parkinsonian. The other study, conducted in collaboration with Beth Fisher, PhD, PT, at USC, was in people who had been diagnosed with PD for less than three years.
Participants were divided into three groups to compare the effects of different levels of exercise. People in the high-intensity group exercised three times a week for an hour on a body-weight supported treadmill — a harness protected them from falling. The second group did low-intensity balance and stretching exercises, which is what most previous studies of exercise in people with PD have evaluated. The third group did no organized exercise at all.
The body-weight supported treadmill combines all the features of exercise that we think are important for driving changes in the brain. The exercise is complex and intense (it moves fast and with high repetition). Participants get feedback from a trainer while they run, so they are simultaneously listening, processing the instructions and adjusting their pace. Exercising on the treadmill is also task-specific: it addresses walking, a functional task that we need in our daily lives.
Over the course of 24 sessions, those in the high-intensity group walked and ran faster than those in the other groups, working up to speeds of five to eight miles an hour. They also took longer strides, better posture and bigger arm swings. As they walked on the treadmill three times a week, for an hour each time, every characteristic of their walking began to look more normal.
Balance was also tested. Though the participants were newly diagnosed and had not yet reported balance problems, it was found — before they exercised — that their balance was not normal. While walking, they made tight turns and they took small constrained steps. After several weeks of treadmill exercise, their turns became more stable. Balance, as well as gait, improved.
How Exercise Changes the Brain
What happens in the brain to produce these visible benefits? To find out, researchers looked at the brains of the mice that had exercised under conditions parallel to the human study.
Researchers found that exercising changed neither the amount of dopamine nor the number of neurons in the animals’ brains. But in the ones that had exercised, the brain cells were using dopamine more efficiently. They found that exercise improves that efficiency by modifying the areas of the brain where dopamine signals are received — the substantia nigra and Area of the brain responsible for producing smooth, continuous muscular actions, including starting and stopping movements; also responsible for elements of thinking..
At the molecular level, at least two things are happening to make dopamine use more efficient. Dopamine travels across a space between two adjacent brain cells called a synapse. This process is called signaling and it is essential for normal functioning. To end the signal, a protein complex called the A protein that modulates how much of the neurotransmitter dopamine is available in the brain. It moves dopamine out of the space between nerve cells (synapse), which ends dopamine’s signaling. normally retrieves dopamine from the synapse.
The first thing found in animals that had exercised was less dopamine transporter, meaning that dopamine stayed in their synapses longer and the signals lasted longer. Second, the cells receiving the dopamine signal had more places for the dopamine to bind in animals that exercised, thus could receive a stronger signal. This binding site is called the D2 receptor. A study was also done of the D2 receptor in a subset of human subjects within one year of diagnosis and not on any medications. It used the imaging technique known as positron emission tomography (PET). It found when humans exercise as well, they also increase the number of D2 receptors.
Lastly, animal studies have shown that intensive exercise may also play a role in controlling glutamate, another molecule that signals between brain cells. Dopamine is responsible for holding glutamate in check, so when dopamine levels drop in PD, a chain of events is set off that leads to a build-up of glutamate signaling. The resulting surplus of glutamate damages the cells that control body movements. Animal studies show exercise may play a role in normalizing glutamate signaling, helping the brain to function normally and promote recovery of the ability to move.
More research is needed to understand which aspects of exercise are most important, whether the benefits are long-lasting and whether drug and other therapies influence its effects. In studying the underlying molecular mechanisms, scientists may find new targets for drug therapies. In the meantime, intensive exercise helps people with PD walk and move better. Research is beginning to reveal how it reconditions the underlying brain circuits.
Page reviewed by Dr. Chauncey Spears, Movement Disorders Fellow at the University of Florida, a Parkinson’s Foundation Center of Excellence.