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

Parkinson’s Stealth: The Decade-long Silent Progress Before Symptoms Arise

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

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

Key Facts:

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

Source: University of Montreal

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

Carried out at the Université de Montréal and published in the journal Nature Communications,  the research sheds new light on the surprising resilience of the brain during the asymptomatic period of Parkinson’s.

In their study, a team led by UdeM neuroscientist Louis-Éric Trudeau demonstrated that 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 initial hypothesis, but that’s often the way it is in science, and it forced us to re-evaluate our certainties about what dopamine really does in the brain,” said Trudeau, a professor in UdeM’s Department of Pharmacology and Physiology and Department of Neurosciences.

Using genetic manipulations, 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 laboratory, Benoît Delignat-Lavaud expected to see a loss of motor function in these mice similar to what is seen in individuals with Parkinson’s.

But surprise! The mice showed a completely normal capacity for movement.

Measuring dopamine levels

Meanwhile, measurements of overall dopamine levels in the brain, carried out by UdeM trauma specialist Louis de Beaumont’s team at the Centre de recherche de l’Hôpital du Sacré-Cœur de Montréal, revealed that extracellular levels of dopamine in the brain 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 dopamine levels in the brain remain sufficiently high for many years – this, despite the gradual loss of dopamine-producing neurons. It is only when a minimum threshold is exceeded that motor perturbations appear.

According to the scientists, by identifying the mechanisms involved in the secretion of dopamine in the brain, this advance in Parkinson’s research could help to identify new approaches to reduce the symptoms of this incurable neurodegenerative disease.

About this Parkinson’s disease research news

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

Original Research: Open access.
Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice” by Louis-Éric Trudeau et al. Nature Communications


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

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

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

Strikingly, Syt1 cKODA mice showed intact performance in multiple unconditioned DA-dependent motor tasks and even in a task evaluating conditioned motivation for food.

Considering that basal extracellular DA levels in the striatum were unchanged, our findings suggest that activity-dependent DA release is dispensable for such tasks and that they can be sustained by a basal tone of extracellular DA.

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

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