A new angle on basic Parkinson’s research

Benoît Delignat-Lavaud
PhD Candidate
Université de Montréal
Graduate Student Award
$20,000 over 2 years
Evaluation of the mechanisms of somatodendric dopamine release and its contributions to post-lesional plasticity in Parkinson’s disease models

Determining the cause of Parkinson’s disease at the cellular level is a complex job, requiring researchers to understand precisely how brain cells function and interact with dopamine, a signalling chemical whose loss results in the typical motor symptoms of this debilitating illness.

At the Université de Montréal, PhD student Benoît Delignat-Lavaud, a neuroscientist, studies the way different parts of the cell release dopamine. Until now, most researchers have focused on dopamine released from the axon terminals – the buttons at the end of the brain cells that signal other neurons, using chemicals like dopamine that control the body’s movement.

When these brain cells die, the dopamine the terminals normally release disappears. Currently, doctors treat Parkinson’s disease by giving people a synthetic form of dopamine, called levodopa, and trying to get the axon terminals to absorb it.

But what if other parts of the cell that also generate dopamine could be persuaded to take over when the cell’s terminals stop working? That’s the hypothesis Delignat-Lavaud is pursuing.

“Therapies right now have limited effectiveness because we are trying to treat something that we don’t understand,” he says. “We have to return to the basics, the physiology of the disease, because it will help us to understand when neurons are starting to die and why.”

Delignat-Lavaud focuses on the release of dopamine from neurons’ dendrites, the branch-like structures that flow from a neuron’s body, which is called the soma.

“Therapies right now have limited effectiveness because we are trying to treat something that we don’t understand,” he says. “We have to return to the basics, the physiology of the disease, because it will help us to understand when neurons are starting to die and why.”

The death of dopamine-producing brain cells starts at the axons, he believes. What’s not well understood is the role the dendrites and soma play in dopamine release and in the death of these cells.

“Something nobody has done before is to record the dopamine release at the level of dendrites and cell bodies in this process,” he says.

Delignat-Lavaud will measure that release in dopamine-producing neurons from brain sections prepared from mice. He’ll also look at how dopamine neurons adapt when they’re exposed to toxins or other stresses that cause the cells to die.

Ultimately, he wants to determine whether enhancing the release of dopamine from the dendrites instead of the cell terminals can help dopamine neurons to cope.

If Delignat-Lavaud can identify proteins that control dopamine release from dendrites, he hopes to be able to persuade different parts of the neurons to compensate for the loss of dopamine in other regions and to find new targets for gene therapy or stem cell transplants.

Delignat-Lavaud is driven by his curiosity about how the brain works, and he enjoys the Parkinson’s field because it is dynamic and constantly evolves.

“The brain is one of the most mysterious organs that remains in the body, and there’s a lot of work that has to be done. It’s like an organ that is trying to understand itself – and that’s fascinating.”