Summary: New findings suggest that Parkinson’s disease can progress quietly for more than a decade before symptoms appear. The study found that motor circuits in the brain can maintain function even when active dopamine secretion is drastically reduced, a phenomenon that is contrary to popular belief.
Dopamine is considered crucial for movement, and its reduction is a hallmark of Parkinson’s disease. These findings may pave the way for new therapeutic approaches to alleviate the symptoms of this neurodegenerative disease.
Key facts:
- The research suggests that Parkinson’s disease can progress for more than 10 years without showing symptoms.
- The brain’s motor circuits have been found to be surprisingly resilient, functioning normally even with an almost complete loss of active dopamine secretion.
- These findings may 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: University of Montreal
Have you or a loved one just been diagnosed with Parkinson’s disease? Well, the disease is likely to progress quietly but insidiously for more than 10 years, new research suggests.
Performed at Université de Montréal and published in the journal Nature Communicationsthe study 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 neuroscientist Louis-Eric Trudeau of UdeM demonstrated that motor circuits in the brains of mice were insensitive to an almost complete 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 contradicts our original hypothesis, but this is often the case in science and forced us to reassess our certainty about what dopamine really does in the brain,” said Trudeau, professor at the UdeM Department of Pharmacology and Physiology and Department of Neuroscience .
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 those cells.
As a postdoctoral fellow in Trudeau’s lab, Benoît Deligna-Lavoux expected to see a loss of motor function in these mice similar to that seen in individuals with Parkinson’s.
But surprise! The mice showed completely normal locomotor capacity.
Measuring dopamine levels
Meanwhile, measurements of total brain dopamine levels carried out by the team of UdeM trauma specialist Louis de Beaumont at the Sacre-Coeur de Montréal Hospital Research Center revealed that extracellular dopamine levels in the brains of these mice were normal.
These results suggest that the activity of motor circuits in the brain requires only low basal levels of dopamine.
Therefore, it is likely that in the early stages of Parkinson’s disease, the basal levels of dopamine in the brain remain sufficiently high for many years – this despite the gradual loss of dopamine-producing neurons. Only when a minimum threshold is exceeded do motor disturbances appear.
According to the scientists, by identifying the mechanisms involved in the secretion of dopamine in the brain, this advance in Parkinson’s research may help identify new approaches to reducing the symptoms of this incurable neurodegenerative disease.
About this Parkinson’s research news
Author: Jeff Heinrich
source: University of Montreal
Contact: Jeff Heinrich – University of Montreal
Image: Image credit: Neuroscience News
Original Research: Free access.
“Synaptotagmin-1-dependent phasic axonal release of dopamine is not required for basic locomotor behavior in mice” by Louis-Eric Trudeau et al. Nature Communications
Summary
Synaptotagmin-1-dependent phasic axonal release of dopamine is not required for basic locomotor behavior in mice
In Parkinson’s disease (PD), motor dysfunctions become apparent only after extensive loss of DA innervation. This robustness is hypothesized to be due to the ability of many motor behaviors to be sustained by a diffuse DA basal 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 cKOAnd mice) abolished most activity-dependent axonal DA release in the striatum and mesencephalon, leaving somatodendritic (STD) DA release intact.
Strikingly, Syt1 cKOAnd mice showed intact performance in multiple unconditioned DA-dependent motor tasks and even in a task assessing conditioned motivation for food.
Given that basal extracellular DA levels in the striatum were unchanged, our findings suggest that activity-dependent DA release is required for such tasks and that they can be sustained by a basal tone of extracellular DA.
Taken together, our findings reveal the striking robustness of DA-dependent motor functions in the context of near-abolition of phasic DA release, shedding new light on why extensive loss of DA innervation is required to reveal motor dysfunctions in PD.