The link between running and dopamine release may have implications for the treatment of Parkinson’s disease

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

“Our results help us understand why exercise improves 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 way to augment or even replace the use of dopamine-increasing drugs in these patients.”

Rice is the lead author of the paper published by the team in Journal of Neurosciencewhich is called “Voluntary exercise stimulates 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 including Parkinson’s disease, depression and anxiety.”

It’s no secret that exercise is good for the brain. Exercise can improve mood, sharpen memory and prevent cognitive decline. It has long been known that regular running increases dopamine activity in the brain and can protect nerve cells from damage. “Exercise has been shown to improve movement and cognition in humans and rodents,” the authors wrote. “Exercise improves motor performance in people with Parkinson’s disease and improves mood in people with depression.”

But while previous research has linked exercise-induced elevation of BDNF levels and dopamine levels to improved learning and memory, the precise way these factors interact is unclear. is unclear.

For their recently reported study, the researchers compared dopamine signaling in mice after 30 days of voluntary running with that of inactive animals. They provided dozens of male mice with unrestricted access to either a freely spinning wheel or a stuck wheel that couldn’t move. After a 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 engineered to produce half as much BDNF as regular mice.

The results showed that normal mice running on a wheel for 30 days had a 40% increase in dopamine release in the dorsal layer, the part of the brain involved in movement, compared to dopamine levels in mice that weren’t exercising. Notably, the increase in dopamine release remained elevated even after a week of rest.

The evoked increase in dopamine release persists even seven days after the end of exercise. [Bastioli et al., JNeurosci 2022]

The investigations also revealed that the running mice had an almost 60% increase in BDNF levels compared to 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 active and sedentary animals, suggesting that BDNF catalyzes increased dopamine signaling.

“Our results 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 at neuroscience department at NYU Langone Santé. “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 don’t exercise every day.”

While researchers have previously measured dopamine activity during running, the new investigation provides insight into the hormone’s long-term behavior and effects on the brain long after exercise has stopped. “Overall, current studies point to underlying factors in the beneficial effects of exercise on motor and reward pathways and may point to new therapeutic options for stimulating 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 the effects of dopamine on motor neurons. However, the mechanism behind the role of dopamine in this protective benefit of exercise had not been fully explored. Their just-published results provide new insights into how exercise could reduce symptoms of Parkinson’s disease, and potentially how exercise could be used in addition to – or potentially as an alternative – to dopamine-stimulating 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 brains. neurotoxin models of PD,” the team commented. “These studies provide insight into the beneficial effects of exercise that could be exploited for therapeutic approaches to PD and other neuropsychiatric disorders.”

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

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

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