Collaborating for a cure

By Jennifer Parraga, BA'93

Vania Prado, PhD, is driven to find answers that will lead to new treatments and even a cure for Alzheimer’s disease. A scientist at Robarts Research Institute, she is passionate about her work and feels invigorated by the growing collaborative research opportunities available at the Institute and Western University.

“I love what I do, and I love the fact that every day I have to learn something new. I just keep reading, asking questions and searching for the proper answers,” Prado said. “My goal is to contribute to the treatment of Alzheimer’s, my dream is to find a cure for this deceptive and crippling disease.”

Prado arrived at Robarts in 2008 with her husband and research partner Marco Prado.
They were no strangers to the Institute, at the time, as they had collaborative research projects with researchers at Robarts.

They didn’t come alone.

Not only were they joined by seven trainees from their homeland of Brazil, but they also brought along a number of genetically modified mice, who are central to Prado’s research.

Prado’s is focused on understanding the role the cholinergic system plays in the regulation of distinct behaviours and what happens when the system malfunctions, as is the case in Alzheimer’s disease.

In her work, Prado uses genetically modified mice that model different neurodegenerative diseases. Some of these mice don’t release acetylcholine in specific areas of the brain and she uses them to explore how brain circuits are affected when acetylcholine is not present. Prado’s lab uses careful molecular, cellular and state-of-the-art behavioural analysis to dissect novel pathways affected in neurodegenerative diseases.

“We have a number of different mouse lines that model different diseases and behaviours, which is making our work very comprehensive,” Prado said.

One of the first findings in the brain of individuals with Alzheimer’s disease is a failure of the system which secretes the neurotransmitter acetylcholine, known as the cholinergic system.

Brain inflammation is also thought to be a critical component in the disease and contributes to worsening memory and behavioural deficits.

Interestingly, Prado’s studies have shown that decreased acetylcholine, as seen in Alzheimer’s disease, exacerbates inflammatory responses in the brain. Thus, her main focus at the moment is to determine how acetylcholine-secreting neurons influence brain inflammatory responses and to explore different alternatives to bypass this failure in acetylcholine-secreting neurons and help to ameliorate brain inflammation.

To do that, she has generated genetically-modified mice in which she can modulate the activity of microglia, the resident immune cells in the brain. She is testing whether activating special microglial receptors, which are similar to some of the receptors activated by acetylcholine, in a mouse model of Alzheimer’s disease improves brain inflammation and some of the critical pathologies found in Alzheimer’s. She is also investigating whether failure of acetylcholine-secreting neurons contribute to the signature pathological changes found in Alzheimer’s disease.

To test cognitive deficits in mice, Prado’s lab uses an automated touchscreen apparatus which is similar to an iPad. Using these mouse touchscreens, invented by her Western colleagues Tim Bussey, PhD, and Lisa Saksida, PhD, it is possible to determine whether the different mouse models are impaired in a number of different cognitive functions. Importantly, the mouse touchscreen tests facilitate translational studies between mice and humans as they are very similar to human tests.

While studies with Alzheimer’s mouse models continues, Prado’s lab, including six graduate trainees, one post-doctoral fellow, three technicians and several visiting trainees, is also investigating and trying to understand the biology of other neurodegenerative diseases and how researchers may help delay onset of them.

Prado believes that research collaborations like those her lab has undertaken at Robarts, at Western University and, in fact, around the world, are more important than ever in research.

“If you want to answer important research questions, you can’t work alone,” she said. “When you incorporate additional expertise to your work, you can answer a lot more questions.”

Ever intrigued and passionate, Prado says it’s nature’s deceiving qualities that keep her focused on finding answers.

“We are really happy and excited about our research, and I believe that we will be able to achieve a great deal with our current studies and collaborations.”