How a lucky accident helped spark a new era of depression research

Dr. Paul Albert is receiving the Grimes Research Career Achievement Award in recognition of his outstanding contributions to neuroscience

October 21, 2019

Dr. Paul Albert“The post-stroke depression model is the first where we’ve seen treatments cause serotonin-producing neurons to regenerate,” said Dr. Paul Albert. “It gives us hope that regenerative approaches may be useful for treating this and other kinds of depression.”It all started with one lucky accident. In the late 1980’s, Dr. Paul Albert was trying to isolate a gene that controls metabolism. Instead, he pulled out a gene that controls motivation and another that controls mood. These two genes became the subject of tens of thousands of studies that have transformed our understanding of the brain.

“The most fun part is when you find something that you never expected,” said Dr. Albert, a senior scientist in the Neuroscience Program at The Ottawa Hospital and professor in the University of Ottawa Brain and Mind Research Institute. “It opens a door to a whole new playground of discovery.”

It turned out that Dr. Albert was the first in the world to isolate the motivation-related gene (called the dopamine receptor) and he tied for the mood-related gene (called the serotonin receptor). These discoveries opened up so many doors that he never went back to his original interest in the metabolic gene.

“First I focused on what these receptors do and how they tell brain cells what to do,” said Dr. Albert, “Then I became interested in what regulates them, because this happens over a lifetime and seemed to be important for depression.”

Dr. Albert went on to discover that people with a certain genetic mutation in the serotonin receptor are more likely to experience depression, less likely to respond to common anti-depressants and more likely to die by suicide. He also discovered exactly how the serotonin receptor and the mutated version worked at the molecular level.  

“Next, we wanted to test if the mutation leads to depression in a mouse model,” said Dr. Albert “And we found that it does.”

Dr. Albert’s team is now exploring novel approaches to treat depression using these mouse models. For example, they are using light to stimulate very specific areas of the brain that are involved in serotonin signaling, with promising results.

“Our techniques aren’t ready for humans yet, but the science is advancing so rapidly that I think we’ll get there eventually,” he said. “This is really important because 70 percent of people don’t respond well to existing anti-depressants.”

Dr. Albert’s team is also looking at post-stroke depression, which affects more than a third of stroke survivors.

“The post-stroke depression model is the first where we’ve seen treatments cause serotonin-producing neurons to regenerate,” said Dr. Albert “It gives us hope that regenerative approaches may be useful for treating this and other kinds of depression.”

Among his colleagues and trainees, Dr. Albert is known as a generous collaborator, a wise mentor and an inspiring leader. He led the Neuroscience Graduate Program at the University of Ottawa for many years, and also serves as Associate Scientific Director of The Ottawa Hospital’s Neuroscience Program and leader of the Neuroscience Seminar Series.

“We have a very collaborative environment here in Ottawa and a really friendly scientific community,” said Dr. Albert. “It has been really rewarding to see so many of our scientists and trainees succeed and make discoveries that could impact peoples’ lives.”

Dr. Albert’s research has been funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation (HSF), the HSF Canadian Partnership for Stroke Recovery, the Parkinson Research Consortium, the Ontario Mental Health Foundation and the Natural Sciences and Engineering Research Council of Canada. All research at The Ottawa Hospital is also supported by The Ottawa Hospital Foundation.

Dr. Albert will be presented with the Grimes Research Career Achievement Award at The Ottawa Hospital Gala on Saturday, October 26, 2019, in recognition of his outstanding contributions to neuroscience.

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Scientific Program tags: Neuroscience Program