New evidence challenges understanding of Parkinson’s disease

(Press-News.org) A McGill-led study is challenging a popular theory about how dopamine drives movement, a discovery that could shift how scientists think about Parkinson’s disease treatments. 

Published in Nature Neuroscience, the research found dopamine does not set the speed or force of each movement, as had been thought. Instead, it appears to act as the underlying support system that makes movement possible. 

“Our findings suggest we should rethink dopamine’s role in movement,” said senior author Nicolas Tritsch, Assistant Professor in McGill’s Department of Psychiatry and researcher at the Douglas Research Centre. “Restoring dopamine to a normal level may be enough to improve movement. That could simplify how we think about Parkinson’s treatment.” 

Dopamine is known to be important for motor vigour, which is the ability to move with strength and speed. In Parkinson’s patients, dopamine-producing neurons deteriorate, leading to slower movement, tremors and balance issues. 

The standard treatment for Parkinson’s, Levodopa, helps restore movement, but why it works is not well understood. In recent years, advanced tools detected fast dopamine spikes during movement, which led many to believe these spikes control vigour. 

The new study points in the opposite direction.  

“Rather than acting as a throttle that sets movement speed, dopamine appears to function more like engine oil. It’s essential for the system to run, but not the signal that determines how fast each action is executed,” said Tritsch. 

Measuring dopamine in real time  The researchers measured brain activity in mice as they pressed a weighted lever, turning dopamine cells “on” or “off” using a light-based technique. 

If fast dopamine bursts did control vigour, changing dopamine at that moment should have made movements faster or slower. To their surprise, it had no effect. In tests with levodopa, they found the medication worked by boosting the brain’s baseline level of dopamine, not by restoring the fast bursts. 

A more precise target for treatment  More than 110,000 Canadians live with Parkinson’s disease, a number projected to more than double by 2050 as the population ages. 

A clearer explanation for why levodopa is effective opens the door to new therapies designed to maintain baseline dopamine levels, the authors note. 

It also encourages a fresh look at older therapies. Dopamine receptor agonists have shown promise but caused side effects because they acted too broadly in the brain. The new finding offers scientists a sense of how to design safer versions. 

About the study  “Subsecond dopamine fluctuations do not specify the vigor of ongoing actions” by Haixin Liu and Nicolas Tritsch et al., was published in Nature Neuroscience. 

The study was funded by the Canada First Research Excellence Fund, awarded through the Healthy Brains, Healthy Lives initiative at McGill University and the Fonds de Recherche du Québec. 

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