University of Montreal
Funded by Quebec Research Fund* on Parkinson of Parkinson Quebec
Pilot Project Grant: $44,240 (one year)
Dopamine neuron axonal arborization size as a target to influence vulnerability and produce better mouse models of Parkinson’s disease.
Understanding why brain cells degenerate is a critical step in identifying new treatments for Parkinson’s disease. To evaluate those new treatments, researchers require animal models to make sure the drugs or gene therapies work as planned and are safe to use in people.
So far, creating an animal model of Parkinson’s has proven elusive. Even when researchers introduce mutated genes known to cause Parkinson’s in humans, those changes do not typically cause Parkinson-like symptoms in mice.
At the University of Montreal, neuroscientist Louis-Eric Trudeau thinks he knows why it has been so difficult to replicate Parkinson’s in mice and other animal models. Trudeau and his colleagues studied the cells in the part of the brain most at risk in Parkinson’s disease, a region called the substantia nigra. They discovered that the axons of these neurons, which produce the chemical transmitter dopamine and play critical roles in regulating movement, have exceptionally complex structures.
Axons are the branch-like structures that make contact with other cells to help them communicate. The dopamine-producing cells in the substantia nigra are much larger and consume much more energy than other cells. That’s the reason Trudeau believes they may be more vulnerable than other cells to whatever process is killing the neurons in Parkinson’s disease.
The size and complexity of these neurons in the mouse brain compared to the human brain may be one of the key reasons current mouse models don’t develop Parkinson’s-like symptoms. The mouse neurons may not be big enough to be vulnerable to the signals that trigger Parkinson’s progression in humans. Trudeau plans to modify the dopamine-producing neurons in a new mouse model, ensuring they grow larger and consume more energy.
“We predict this will allow us to make a mouse model in which the dopamine neurons will be more vulnerable, in a way more similar to what we see in the human brain,” Trudeau says.
If Trudeau succeeds in creating a better mouse model, it will not only allow researchers to test new drugs and treatments, it will also enrich their understanding of the reasons dopamine-producing brain cells die, causing Parkinson’s.
“For all major diseases of the brain, new therapies come after we know why the cells start to die,” Trudeau says.
* Quebec Research Fund on Parkinson is funded notably, by the Saucier-van Berkom Parkinson Quebec Research Fund