Researchers from McGill and Western University are using innovative animal models to investigate links between stress and Alzheimer’s Disease
The McGill-Western Collaborative Grant Program currently supports seven research teams working in neuroscience and neuroinformatics. This program was created to take full advantage of the combined total of $150 million in funding awarded to the two institutions by the Canada First Research Excellence Fund through Healthy Brains, Healthy Lives (HBHL) and BrainsCAN.
One collaborative project, led by McGill’s Dr. Mallar Chakravarty and Western’s Dr. Tim Bussey, uses cutting-edge animal models to investigate how stress experienced in middle age can contribute to the development of Alzheimer’s Disease. Since there are currently no effective treatments for Alzheimer’s, projects like this one are critical to understanding how to prevent the disease.
The research team uses magnetic resonance imaging (MRI) to examine how a mouse’s brain structure changes in response to stressful situations and environments. Rather than the typical approach of recording data from mice as they complete simple tasks like navigating a maze, the animals interact with a touchscreen to complete complex tasks. “This is where our collaboration with the group at Western University becomes very important,” Dr. Chakravarty explains. “They’re really pioneers in new types of behavioural analysis that allow you to get a very impressive readout of mouse behaviour in relation to cognitive tasks that are modelled and patterned after well-used, well-defined cognitive tasks—typically used in humans in clinical populations. The cool thing is that these mice learn how to navigate a touchscreen. The mice know they’ve done the task correctly when they get a little milkshake reward.”
After putting the mice through touchscreen tasks, the team combines the imaging data and readouts of mouse behaviour with RNA sequencing data. Samples from specific areas of the brain are used to better understand how genes are working in those regions. “This approach allows us to investigate how the brain alterations we’re studying occur, link them to behaviours we can observe and, ultimately, connect them to molecules that might drive all these changes,” says Dr. Chakravarty. “We think this multidisciplinary approach is really exciting—we can chase avenues of research and questions that we weren’t able to before and come up with collaborations that will benefit science, benefit treatments and benefit our understanding of how the brain works in the next five to ten years.”
Currently, data gathered through the touchscreen platform is uploaded to MouseBytes, an open access platform developed by the Western BrainsCAN Rodent Cognition Core. A further goal of the project is to expand this existing infrastructure to also integrate MRI and RNA sequencing data, as Dr. Bussey explains. “Following some further coding work at Western and McGill, integrated behavioural, imaging, and RNA sequencing data will be able to be deposited, stored, shared and reanalysed by researchers, including those in the over 300 touchscreen labs around the world. This is one of the most comprehensive and interdisciplinary Open Science projects ever attempted.”
Dr. Chakravarty emphasizes that this project wouldn’t have been possible without the joint HBHL/BrainsCAN call for applications that required collaborations between researchers at McGill and Western. “Dr. Bussey and I hadn’t really worked together before. This project allows my lab to collaborate with the neuroscience group at Western using our tools in a way that we didn’t before,” he explains. “We’ve also had trainees go visit Western’s site on multiple occasions to learn how to use the touchscreen platform and really mine the rich source of data that it provides. They’ve also sent trainees over to our McGill lab, where we teach them about our work in imagining and imaging analysis.”
According to Dr. Chakravarty, one value add of HBHL is its flexibility in funding innovative new research programs. “This type of grant is generally something that’s not typically funded by more conventional funding bodies. I think this is a very important aspect of what HBHL has been able to do, is allow us to build new platforms and technologies, rather than have the technologies in place so we can ask scientific questions. I think that’s a really important aspect of what HBHL has allowed my lab to do to, especially in the context of this work.”
April 2 2020