The Stealth of Parkinson’s Disease: The Silent Progress of a Decade Before Symptoms Appear

Summary: New findings suggest that Parkinson’s disease can progress silently for more than a decade before symptoms appear. The study found that movement circuits in the brain can maintain their function even with a drastic reduction in active dopamine secretion, a phenomenon contrary to popular belief.

Dopamine is considered crucial for movement and its decrease is a hallmark of Parkinson’s disease. These discoveries could pave the way for new therapeutic approaches to relieve the symptoms of this neurodegenerative disease.


  1. Research suggests that Parkinson’s disease can progress for more than 10 years without showing symptoms.
  2. The brain’s movement circuits were found to be surprisingly resilient, functioning normally even with an almost complete loss of active dopamine secretion.
  3. These findings could lead to new methods of treating the symptoms of Parkinson’s disease by understanding the mechanisms involved in the secretion of dopamine in the brain.

Source: Montreal university

Have you or someone close to you just been diagnosed with Parkinson’s disease? Well, chances are the disease has been progressing quietly but insidiously for more than 10 years, according to new research.

Produced at the University of Montreal and published in the journal Nature Communicationresearch sheds new light on the surprising resilience of the brain during the asymptomatic period of Parkinson’s disease.

In their study, a team led by UdeM neuroscientist Louis-Éric Trudeau demonstrated that the movement circuits in the brains of mice are insensitive to an almost total loss of active secretion of this chemical messenger.

This observation is surprising because dopamine is a chemical messenger recognized for its importance in movement. And in Parkinson’s disease, dopamine levels in the brain drop inexorably.

“This observation went against our original hypothesis, but that’s often how it is in science, and it forced us to reevaluate our certainties about what dopamine actually does in the brain,” said Trudeau, professor in the Department of Pharmacology and Pharmacology at UdeM. Physiology and Department of Neurosciences.

Using genetic manipulation, Trudeau and his researchers eliminated the ability of dopamine-producing neurons to release this chemical messenger in response to the normal electrical activity of these cells.

As a doctoral student in Trudeau’s lab, Benoît Delignat-Lavaud expected to see a loss of motor function in these mice similar to what is seen in people with Parkinson’s disease.

But surprised! The mice showed completely normal ability to move.

Measure dopamine levels

At the same time, measurements of overall levels of dopamine in the brain, carried out by the team of UdeM traumatologist Louis de Beaumont at the Research Center of the Hôpital du Sacré-Coeur de Montréal, revealed that the extracellular levels of dopamine in the brains of these mice were normal.

These results suggest that the activity of movement circuits in the brain requires only low basal levels of dopamine.

It is therefore likely that in the early stages of Parkinson’s disease, basal levels of dopamine in the brain remain sufficiently high for many years, despite the progressive loss of dopamine-producing neurons. It is only when a minimum threshold is exceeded that motor disturbances appear.

By identifying the mechanisms involved in the secretion of dopamine in the brain, this breakthrough in Parkinson’s disease research could help identify new approaches to reducing the symptoms of this incurable neurodegenerative disease, say the scientists.

About this Parkinson’s disease research news

Author: Jeff Heinrich
Source: Montreal university
Contact: Jeff Heinrich – University of Montreal
Picture: Image is credited to Neuroscience News

Original research: Free access.
Synaptotagmin-1-dependent phasic axonal dopamine release is essential for basic motor behaviors in miceby Louis-Éric Trudeau et al. Nature Communication


Synaptotagmin-1-dependent phasic axonal dopamine release is essential for basic motor behaviors in mice

In Parkinson’s disease (PD), motor dysfunctions become apparent only after a significant loss of DA innervation. This resilience has been hypothesized to be due to the ability of many motor behaviors to be maintained by diffuse basal DA tone; but experimental evidence for this is limited.

Here, we show that conditional deletion of the calcium sensor synaptotagmin-1 (Syt1) in DA neurons (Syt1 cKOAD mouse) abrogates the most activity-dependent axonal DA release in the striatum and midbrain, leaving somatodendritic DA (STD) release intact.

Surprisingly, Syt1 cKOAD the mice showed intact performance in several unconditioned DA-dependent motor tasks and even in a task assessing conditioned motivation for food.

Considering that basal levels of extracellular DA in the striatum were unchanged, our results suggest that activity-dependent DA release is indispensable for such tasks and that they may be supported by basal tone of extracellular DA.

Taken together, our results reveal the striking resilience of DA-dependent motor functions in the context of near-abolition of phasic DA release, shedding new light on why a significant loss of DA innervation DA is needed to reveal motor dysfunctions in PD.

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