For Canada's 150th Birthday, my research was profiled in the Faces of Health Research, by the Canadian Institutes of Health Research (CIHR).
Dr. Nafisa M. Jadavji
Vascular cognitive impairment (VCI) is the second leading cause of dementia after Alzheimer's disease. The clinical presentation of VCI varies and there are no treatments for VCI since the actual pathology remains unknown. Nutrition is a risk factor for VCI, specifically high levels of homocysteine, a common amino acid in blood. B vitamins, such as folic acid, can reduce levels of homocysteine.
My research program focuses on how nutrition affects the brain. Our results suggest that it is not elevated levels of homocysteine making the brain more vulnerable to VCI, but rather, a deficiency in folic acid. In the cell, folic acid is involved in essential functions that help the cell survival.
Reduced levels of folic acid may be changing the cells in the brain, making them more vulnerable to damage. More research is required to understand how nutrition can be used to promote healthy brain aging.
This blog post was written for AlzScience, in 2017. It describes in lay term my
High levels of homocysteine have been implicated in neurodegenerative diseases, such as dementia, mild cognitive impairment, and Alzheimer’s disease. Homocysteine can be measured in blood easily, which has led to several studies in humans reporting that elevated levels of homocysteine lead to increased risk of developing neurodegenerative diseases or affect progression. Interestingly, homocysteine levels in our bodies increase as we age.
Vascular cognitive impairment (VCI) is the second leading cause of dementia after Alzheimer’s disease. VCI is the result of reduced blood flow to the brain, however, the pathology is not well understood. Reduced blood flow ben be a result of age and health (e.g. high cholesterol). The clinical presentation of VCI varies, most the patients have some degree of cognitive decline. There are currently no treatments for VCI since the actual pathology remains unknown.
Nutrition is a risk factor for VCI, specifically high levels of homocysteine. High levels of homocysteine can be reduced by B-vitamins, like folates or folic acid. Folates are the natural occurring form of the vitamin, these are often found in food such as green leafy vegetables or liver. Whereas folic acid is the chemically synthesized form that is often taken in supplemental form.
My research program focuses on how nutrition affects the brain, specifically how folates affect neurodegeneration.
Using a mouse model of VCI we have reported that deficiencies in folates, either dietary or genetic, affect the onset and progression of VCI. Using the Morris water maze task, we report that mice with VCI and folate deficiency performed significantly worse compared to controls. We assessed changes in the brain using MRI and interestingly found that folate deficiency changed the vasculature in the brain of mice with VCI. Because of either a genetic or dietary folate deficiency, all the mice had increased levels of homocysteine. However, we did not observe any significant association between elevated levels of homocysteine and behavioral impairment or changes in the brain tissue of VCI affected mice.
Our results suggest that it is not elevated levels of homocysteine making the brain more vulnerable to damage, but the deficiency in folates, either dietary or genetic that changes the brain. In the cell, folates are involved in DNA synthesis and repair as well as methylation. These are vital functions for normal cell function. Therefore, reduced levels of folate may be changing the cells in the brain and making them more vulnerable to any types of damage. I would like to suggest that high levels of homocysteine may just be out put measurement of some sort of deficiency (e.g. reduced dietary intake of folates). Several studies using brain cells that are grown in petri dishes have reported that extremely high levels of homocysteine need to be added to cells to cause damage. These levels are usually not observed in humans.
In terms of future directions, more research is required to understand how deficiencies in folates, homocysteine and other nutrients that reduce levels of homocysteine like choline change cells in the brain throughout life and how these changes are related to neurodegeneration.
This post was originally published in 2017 for a colleagues WOMEN in STEM website.
1. What is your work/research topic?
My research focuses on nutrition and brain function. I focus on investigating and understanding how dietary and genetic deficiencies in folate metabolism affect the course of neurodegeneration.
2. What was your best day of science?
I don’t have a specific day; I absolutely love when I see my published work comes up on my PubCrawler or GoogleAlert e-mail alerts. I always think, wow all this work I am doing is contributing to something bigger. Sometimes getting caught up in the daily grind makes me forget the bigger picture.
3. What was your worst day in science?
Being told that I was not good enough nor was my research by two different supervisors. Each time it took me over 6 months to recover, but here I am stronger than ever.
4. What is your favorite piece of technology or equipment you get to use in your job?
I have two pieces of technology I love. The first is my MacBook. I can use it to get so much done (e.g. writing, data analysis, marking, e-mails, making figures, editing my website, etc), it doesn’t matter where I am. In terms of laboratory equipment, I love the Qiagen Tissue Lyser, it makes tissue lysing super easy. All samples are treated the same during the lysing process and it’s super-efficient. I never thought I would like a piece a laboratory equipment so much.
1. Where did you grow up?
I grew up in Calgary, Alberta in Canada.
2. What profession did you think you would be when you were a kid?
I always loved science, so I knew I would do something in science. I think my mom wanted me to be a medical doctor, so I guess I sort of accomplished that with my PhD.
3. What do you do to relax outside of lab?
I love to travel and am a huge movie watching fan. I also love to cook and bake. My recent baking feat was gluten free donuts.
4. Do you have any pets?
No pets yet, maybe a dog one day?
5. Do you have any fun hobbies?
In 2015 I took up knitting and I enjoy it a lot. It’s a great mental break from the demanding job of being in science and relaxes me. I have also met some very interesting people since I have started knitting.
6. If you want to talk about your family, what is your family life? How did your family develop alongside your career?
I have not had a chance to develop a family alongside my career. I am working on it. I experienced some significant health challenges at the end of my PhD, but things are finally looking up so I am hoping to start a family soon.
1. What is your best advice for girls interested in science?
You need a thick skin in science, people can be mean and experiments will fail. If you love it, don’t stop because you are told you are not good enough or experiments aren’t going well. Take a step back and rethink things. Flexibility and persistence are key ingredients for success in science.
2. Is there any one event or person who/that made you want to be a scientist?
I remember in my grade 12 biology class we learned about the synapse, specifically the neuromuscular junction and I was like wow, that super cool and I want to learn more. I pursued a BSc in Neuroscience at the University of Lethbridge.
3. Why were your drawn to science? Did you ever consider another career path?
Science always challenges you, it pushes you to learn and do more, which I love. Yes, during the hard times I considered walking away and working at bakery or a flower shop.
4. What was your biggest challenge during your degree?
I experienced significant health problems at the end of my PhD, I went from being very healthy to sick. It was a very challenging time as I was finishing experiments, writing my thesis and preparing ethics applications for my postdoc work in Germany, as well as dealing with my health.
5. What was your biggest motivation to obtain your PhD?
I enjoyed doing the research.
6. If you left academia, what was the biggest hurdle you had moving to industry/other?
Not being able to make my own schedule and do the research I am passionate about.
1. What is your favorite book?
Harry Potter series.
2. What is your favorite desk snack?
Lindt Dark Chocolate and plan rice cakes.
3. What would you listen to while writing?
I like listening to classical music while I am writing, either on the CBC or GooglePlay Music. It helps me focus on writing. I don’t like writing in silence.
4. What color socks are you wearing?
I dislike socks. When I am wearing socks, they are usually black.
5. Any other fun facts about you….
I use to teach and play the piano. I lived in Berlin, Germany for 2 years.