Investigating vulnerable brain cells

Jean-François Poulin quit school and was working at L’Arche Greater Vancouver, a community for adults with development disabilities, when he found his calling as a neuroscientist.

Working with the residents at L’Arche – including one man with Parkinson’s disease – made him realize how extraordinary our brains are, “and how we don’t understand what’s going on in them,” Poulin says.

His desire to help people with brain disorders led him back to university and a career in neuroscience.

“The big goal at first was just to understand what’s going on in our heads,” he says.

Today, Poulin investigates what is going on in our heads at the cellular level. He’s already identified different types of dopamine-generating brain cells. When these cells that produce the signalling chemical dopamine die, the symptoms of this progressive brain disease appear.

Poulin believes one specific type of dopamine neuron is more vulnerable to Parkinson’s than others. Now he’s determining exactly what makes these cells more susceptible.

“A big question in Parkinson’s disease is why are some types of neurons dying and degenerating while others are fine and unaffected, even if the disease-associated proteins are present in all of the neuron.”

He’s concentrating on the junction between cells – called the synapses – and the terminals at the end of the axons, or long cables, that protrude from each cell and carry neurotransmitters, including dopamine.

Making and releasing dopamine takes a lot of energy, Poulin says.

He’s testing the theory that these vulnerable neurons have more synaptic terminals, work harder than the other dopamine cells, and break down with age.

Working with a mouse model, Poulin will over-express alpha-synuclein – a protein implicated in the death of these cells – and see if the neurons with the greatest number of synapses are more affected than the other ones.

If Poulin is right, identifying these more vulnerable cells and their genes will open an avenue to manipulating those genes in the future to make them less vulnerable to the process causing Parkinson’s disease.

“A big question in Parkinson’s research is why are some types of neurons dying and degenerating while others are fine and unaffected, even if the disease-associated proteins are present in all of the neurons,” Poulin explains.

As a fundamental scientist, Poulin is driven by his desire to design experiments to answer questions he doesn’t understand.

“There are many black holes and blank spots that we just don’t know the answers to, and that’s where the fun of science comes in.”