Linking Exercise to Dopamine and Motor Performance in Parkinson Disease

Age-related decline in mobility and coordination is a hallmark of normal aging and is further exacerbated in neurodegenerative conditions such as Parkinson disease (PD), where progressive loss of dopaminergic neurons leads to bradykinesia, rigidity, and impaired balance. While aerobic exercise has long been associated with symptomatic benefits in PD, the neurochemical mechanisms linking physical activity to improved motor performance have remained incompletely understood, particularly in the aging brain.

In newly published research, Margaret Rice, PhD, and colleagues provide direct neurochemical evidence that aerobic exercise robustly enhances dopamine release in both male and female aging mice, with corresponding improvements in coordination and movement speed. The findings, published in npj Parkinson’s Disease, suggest that exercise-induced dopamine release may represent a biologically meaningful mechanism underlying motor benefits observed clinically, with potential implications for therapeutic strategies in PD and other movement disorders.

NeurologyLive® caught up with Rice following her publication to discuss the motivations of the study and the neurochemical basis behind exercise-related improvements in mobility and coordination, with a focus on dopamine signaling in the aging brain. In this Q&A, she explained how her team linked aerobic activity to enhanced dopamine release and motor performance, and explores what this means for PD care. Rice, a professor in the Departments of Neurosurgery and Neuroscience at NYU Grossman School of Medicine, also outlined how these findings could inform future therapeutic strategies and ongoing research in genetic and neurodegenerative models.

What were the biggest takeaways and clinical implications from your study? 

Margaret Rice, PhD: The benefits of exercise in older adults are well recognized to enhance memory and cognitive function and also to improve motor ability. Exercise-based improvements in mobility can be particularly striking for those with Parkinson’s disease, with benefits seen from a range of exercises from walking or running to cycling, dancing, and boxing.

The long-term goal of our research is to uncover factors underlying improved mobility after aerobic exercise. In this study, we began at the beginning by testing the hypothesis that exercise might enhance release of the key motor system neurotransmitter, dopamine. Dopamine is depleted progressively in PD, causing patients with PD to move increasingly slowly, and with increasingly small movements.

We tested this hypothesis in aging male and female mice and indeed found that after 30 days of voluntary wheel-running exercise, brain dopamine release was enhanced by up to 50%. Interestingly, females ran more than twice as far as males each day, but yet the increases in dopamine release were comparable, indicating that a certain level of activity is enough to have this benefit. Fun fact: female runners also ate significantly more each day than sedentary females or either group of males and yet maintained their starting weight. Increased dopamine release was also associated with faster movement in an open arena and shorter times to descend a vertical pole – demonstrating improved mobility and coordination.

Thus, increased dopamine release is a likely contributing factor in exercise benefits on mobility, independent of age or sex. The immediate clinical implication is that healthcare providers have a solid basis for prescribing an exercise regimen for aging patients, with or without a movement disorder diagnosis.

Regarding the connection between dopamine preservation and improved motor function, how can we build on this knowledge?

It has been known since Arvid Carlsson’s pioneering work in the 1950’s (for which he received the Nobel Prize for Physiology and Medicine in 2000) that dopamine loss leads to immobility and that dopamine replacement using levodopa, a dopamine precursor, can restore the ability to move. Levodopa remains the primary treatment available for PD. Our findings support the use of exercise as an adjunct therapy to levodopa that provides a natural way to augment the efficacy of this or other dopamine-related drugs by enhancing dopamine release and signaling. Ultimately, we want to understand the steps between aerobic exercise and increased dopamine release. Identifying factors involved could provide new therapeutic options for PD or other conditions involving decreased mobility.

It’s been known that exercise is good for patients with PD, but what else do we not know about the effects of exercise or the proper way to use it? 

What we didn’t know is that aerobic exercise can boost dopamine release. Our data provide an explanation that health care providers can use to encourage patients with PD to take on an exercise routine. As I already mentioned, many types of exercise show benefits. Studies in patients are still ongoing to define optimal parameters, including how long and how intense the exercise needs to be to have positive effects. Even if general parameters are identified, it is unlikely that there will be a one-size-fits-all exercise regimen to prescribe. This will need to be tailored to individual abilities, the stage of Parkinson’s, and what the patient likes to do. As my colleague Wendy Suzuki at NYU has said, the best exercise is the one you will do!

Are there ways to tailor exercises for older patients with the disease who struggle with movement? 

The Parkinson’s Foundation has an infographic on their website that presents exercises for patients with PD. (https://www.parkinson.org/sites/default/files/documents/parkinsons-exercise-recommendations-infographic.pdf)

I have adapted this to be more general for older individuals:

Additional consideration for older exercisers is that any exercise:

1) May require adaptations for posture, osteoporosis, and pain.

2) Staying mindful of safety for balance and other health problems; Making sure to hold on to something stable as needed. As well as knowing that supervision may be required.

Discuss your next steps in this research - what do you hope to achieve by studying genetically engineered models? 

We have three ongoing next-step projects. The first is to examine the benefits of exercise in a mouse model of PD. Although PD is idiopathic in a majority of patients, 10-15% of patients have a genetic link with a mutation in a gene linked to Parkinson’s. We are collaborating with a group headed by Prof. Jenny Sassone at the Vita-Salute University & San Raffaele Scientific Institute in Milan who developed a mouse line that expresses the most common genetic mutation seen in early-onset PD. This is the Prkn gene that makes parkin protein, and the specific mutation is PrknR275W. Unlike many other genetic mouse models, these mice show dopamine neuron loss by early middle age, decreased dopamine release, and impaired motor performance.

Our results so far show that at ages when these mice show dopamine loss, 30 days of aerobic exercise leads to increased dopamine release and improved mobility, as we saw in wild-type mice. Interestingly, female Prkn mice also run twice as much as males.

A second project is examining factors that contribute to enhanced dopamine release. Previous studies of memory improvement after exercise found that this required brain-derived neurotrophic factor (BDNF), an essential growth factor for brain development. This can be studied in mice that are heterozygous for genetic deletion of BDNF (BDNF-hets); mice with complete loss of BDNF do not live to adulthood, given the essential role of this growth factor in brain development. We found previously that young male BDNF-het mice show no change in striatal dopamine release after 30 days of wheel running exercise. We are not investigating whether BDNF also plays a similarly necessary role in aging mice of both sexes. If so, this would point to a brain signaling pathway that might be harnessed therapeutically to boost dopamine release.

The third project is to test the hypothesis that exercise increases the number of active release sites in dopamine axons using immunohistochemistry with confocal microscopy. If this is seen, we will also examine whether this is also seen in our Parkinson’s model mice, PrknR275W, but absent in BDNF-hets.

Transcript edited for clarity.

REFERENCE
1. Bastioli G, Mancini M, Patel JC, et al. Voluntary exercise increases striatal dopamine release and improves motor performance in aging mice. Npj Parkinson’s Dis. 2025;345.11. doi:10.1038/s41531-025-01213-7