Research in mice has shown how exercise increases levels of a chemical called brain-derived neurotrophic factor (BDNF), which bolsters the release of the “feel-good” hormone dopamine (DA). DA is known to play a key role in movement, motivation, and learning. The researchers, headed by a team at NYU Grossman School of Medicine, say their findings could feasibly help to explain why exercise eases symptoms of Parkinson’s disease.

“Our results help us understand why exercise alleviates the symptoms of Parkinson’s disease, as well as those of neuropsychiatric disorders such as depression,” said neuroscientist Margaret Rice, PhD. “Now that we know why physical activity helps, we can explore it as a means of augmenting or even replacing the use of dopamine-enhancing drugs in these patients.”

Rice is senior author of the team’s published paper in Journal of Neuroscience, which is titled, “Voluntary Exercise Boosts Striatal Dopamine Release: Evidence for the Necessary and Sufficient Role of Brain-Derived Neurotrophic Factor.” In their report the team concluded, “Together, these data support a causal role for BDNF in exercise-enhanced striatal DA release and provide mechanistic insight into the beneficial effects of exercise in neuropsychiatric disorders, including Parkinson’s, depression, and anxiety.”

It’s no secret exercise is good for the brain. Working out can improve mood, sharpen memory, and stave off cognitive decline. Its long been recognized that regular running raises dopamine activity in the brain and may protect nerve cells from damage. “Exercise has been shown to improve movement and cognition in humans and rodents,” the authors wrote. “Physical exercise improves motor performance in individuals with Parkinson’s disease and elevates mood in those with depression.”

But while prior research has linked exercise-driven elevation in levels of the dopamine-triggering chemical BDNF and levels of dopamine to improvements in learning and memory, the precise way that these factors interact hasn’t been clear.

For their newly reported study the researchers compared dopamine signaling in mice after 30 days of voluntary wheel running with that in inactive animals. They provided dozens of male mice with unlimited access to either a freely rotating wheel or a locked wheel that could not move. After one month, the team measured dopamine release and levels of BDNF—a protein involved in neuron health—in the dorsal striatum (DStr) region of the brain slices. They also repeated this same process on a different group of rodents, some of which had been genetically modified to produce half as much BDNF as regular mice.

The results showed that normal mice running on a wheel for 30 days exhibited a 40% increase in dopamine release in the dorsal stratium, the part of the brain involved in movement, when compared with dopamine levels in the mice that did not exercise. Notably, increase in dopamine release remained elevated even after a week of rest.

Increased evoked dopamine release persists even seven days after exercise ends. [Bastioli et al., JNeurosci 2022]
The investigations also found that running mice demonstrated a nearly 60% increase in BDNF levels compared with their non-running counterparts. But when the experiments were repeated in the genetic mouse model lacking BDNF there was no difference in dopamine release between the active and sedentary animals, suggesting that BDNF catalyzes increased dopamine signaling.

“Our findings suggest that BDNF plays a key role in the long-lasting changes that occur in the brain as a result of running,” said study first author and neurobiologist Guendalina Bastioli, PhD, who is a postdoctoral fellow in the department of neuroscience at NYU Langone Health. “Not only do these results help explain why exercise makes you move, think, and feel better, they also show that these benefits continue even if you do not work out every day.”

While researchers have previously measured dopamine activity during running, the new investigation provides insight into the longer-term behavior of the hormone and its effects on the brain well after exercise stops. “Overall, the present studies indicate underlying factors in the beneficial effects of exercise in motor and reward pathways and may point to new therapeutic options to boost DA release,” they wrote.

The study authors noted that patients with Parkinson’s disease and other movement disorders are often treated with drugs that mimic dopamine’s effects on motor neurons. However, the mechanism behind dopamine’s role in this protective benefit of exercise had not been thoroughly explored. Their results just published provide new insights into how exercise might reduce the symptoms of Parkinson’s disease, and potentially how exercise might be used in addition—or potentially alternative—to dopamine-boosting drugs. “Interest in the influence of exercise on brain health is long-standing, with a large literature showing not only improvements in cognition but also preservation of DA neurons and motor activity in neurotoxin models of PD,” the team commented. “These studies provide insight into the beneficial effects of exercise that could be harnessed for therapeutic approaches for PD and other neuropsychiatric disorders.”

Rice, a professor in the departments of neurosurgery and neuroscience and physiology at NYU Langone, cautions that while the preliminary findings in rodents were promising, future studies in humans will be required to fully understand the role of BDNF and dopamine in Parkinson’s disease. And as the team concluded “Our findings support the idea that enhanced DA release not only contributes to improvement in motor symptoms seen with exercise in PD patients but might also underlie alleviation of symptoms in other neuropsychiatric disorders, including depression and anxiety.”

The team also plans to investigate the relationship between exercise, dopamine, and BDNF in female mice, which notably run more frequently than do males. In addition, the researchers intend to directly examine whether active mice have improved motor skills compared with those undertaking only limited physical activity.

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