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This blog post was published on the American Society for Nutrition, in May 2018.
A stroke occurs when there is reduced blood flow to the brain. Blood carries oxygen and glucose to cells in the brain. When there is reduced levels of blood, these cells start to die. Since the brain controls behavior, this cell death leads to impairments in function. The impairments are dependent on where the stroke happens in the brain. There are two main types of stroke, hemorrhagic and ischemic. For this blog, I will be focusing on ischemic stroke which is a result of blockage in a blood vessel. Currently, stroke affects older individuals and the global population is aging according to the United Nations. Additionally, older individuals also lose their ability to absorb all the vitamins and nutrients they require from their diet as they age. Nutrition is a modifiable risk factor for diseases of aging. For example, B-vitamins absorption decreases as individuals age. B-vitamins play a major role in reducing levels of homocysteine, a non-protein amino acid. High levels of homocysteine have been associated with increased risk to develop cardiovascular diseases, such as stroke. Supplementation with B-vitamins has been reported to have positive effects on brain health. A study by researchers in Oxford University and University of Oslo has shown that B-vitamin supplementation in the elderly within the United Kingdom reduced age-related brain atrophy after 2 years of supplementation. Furthermore, another study by the same group reported that B-vitamin supplementation reduced cerebral atrophy in areas vulnerable to Alzheimer’s disease. More recently, a group from China reported that folic acid supplementation in combination with Enalapril, used to treat heard disease, reduced the risk of stroke by 21% in patients that were hypertensive. Within the aging population, B-vitamin supplementation has been reported to have positive effects on brain health. The elderly are more prone to ischemic stroke, but the mechanisms through which this benefit accomplished is not well understood. A recent study investigating the role of B-vitamin supplementation on ischemic stroke was published in the Neurobiology of disease. This study tried to examine the mechanisms of how supplementation improved brain function. A group of wildtype males were put on a folic acid deficient diet (0.2 mg/kg) prior to ischemic damage to increase levels of homocysteine and another group of mice were put on a control diet (2mg/kg folic acid). After ischemic damage to the sensorimotor cortex, FADD mice were put on a supplemented diet, where levels of folic acid, riboflavin, vitamin B12, and choline were increased. Animals were maintained on the diets for 4-weeks after which motor function was assessed. Researchers found that supplemented diet mice performed better on motor tasks compared to CD mice with ischemic damage. In the brain tissue increased levels of plasticity and antioxidant activity were reported. Combination therapies for stroke affected patients are thought to be most effective. A pharmaceutical in combination with a life style change, such as increase exercise may be beneficial for stroke affected patients. This data suggests that nutrition may also be a viable option for life style change ischemic damage.
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This text was originally published on Current Exchange: a blog by CHSL Meeting & Courses.
Meet Nafisa M. Jadavji of Carleton University (Canada). Nafisa is a postdoctoral fellow in Patrice Smith’s lab and a course instructor in the Department of Neuroscience. She returned to the Banbury Campus to participate in the three-day Workshop on Leadership in Bioscience to help her be “better prepared for [her] near-future role.” What are your research interests? What are you working on? My research uses a mouse model to assess how nutrition affects neurological function over the lifespan. I am presently concentrating on neurodegeneration associated to stroke and dementia. My own research group will continue to work on this as well as incorporate the impact of maternal nutrition contributions on long-term offspring neurological function. How did you decide to make this the focus of your research? My scientific training in the field of neuroscience started in 2002. In 2008, during my PhD with Dr. Rima Rozen’s laboratory at McGill University, I began studying – and fell in love with – how nutrition impacts brain function and I have been contributing to the field since. How did your scientific journey begin? I really enjoyed my high school science classes. During my 11th grade biology class, I learned about the brain – specifically what the synapse and neuromuscular junction are and their function – and I became fascinated with how the brain works to control our behaviours. This lead me to pursue neuroscience at the University of Lethbridge where, in 2002, I also got involved in basic research and never left. Was there something about the Workshop on Leadership in Bioscience that drew you to apply? As a Neuroscientist I think my training as a scientist has been extensive. However, when it comes to learning how to lead a research group and manage people, I know I lack that training. The topics covered during the workshop are very applicable to recruiting, as well as running a successful and productive research group which will be helpful to me when I start my research group . What is your key takeaway from the workshop? Being the leader of a laboratory is hard work but the workshop and the tools it gave me have helped me to feel better prepared for my near-future role. What and/or how will you apply what you’ve learned from the Workshop to your work? Carl Cohen, the instructor, provided extensive details about interviewing potential candidates (e.g. graduate students or postdocs). He gave us tools to help make the hiring process more consistent for candidates by introducing us to score sheets for each component of the hiring process (e.g. CV, phone interview, reference checks). I will be using these score sheets and guides as I recruit staff and students for my research group. How many CSHL courses/workshops have you attended? I also attended the Scientific Writing Retreat in 2016. I enjoyed the two courses I have attended and am open to attending more in the future, as well as sending my students and staff to future CSHL courses. If someone curious in attending a future iteration of the Workshop on Leadership in Bioscience asked you for feedback or advice on it, what would you tell him/her? I would recommend the workshop to anyone who plans to hire and manage people in a scientific setting. Though highly-motivated graduate students may benefit from this course, I think senior postdocs and people who have recently started their own independent group would gain the most from the course. What do you like most about your time at CSHL's Banbury Campus? I am runner and the Banbury Campus is a great place to go on an early morning run. I also enjoyed having meals with the other participants. Nafisa received financial support from the Howard Hughes Medical Institute (HHMI) to cover a portion of her course tuition. On behalf of Nafisa, thank you to HHMI for supporting and enabling our young scientists to attend a CSHL course where they expand their skills, knowledge, and network. Thank you to Nafisa for being this week's featured visitor. Folic acid is a B-vitamin and is well known for its role during early neurodevelopment. It promotes the closure of the neural tube in utero. The neural tube in the developing embryo is the first step to forming the brain and spinal cord during in utero neurodevelopment. If the neural tube does not close, it leads to neural tube defects (NTDs) in babies, such as spina bifida (Lemire, 1988). Women of child bearing age are recommended to take 0.4 -1 mg of folic acid supplements daily. Additionally, to reduce the number of NTDs mandatory folic acid fortification laws were put into place in 1998 in the US and Canada, as well as other countries. Since 1998, there has been a reduction in the number of NTDs in both Canada and the US (Castillo-Lancellotti et al., 2013).
The brain begins developing a few days after implantation and continues until the individual is in his or her mid-twenties. During neurodevelopment, the short-term impact of folic acid is well known, but the long-term effects are not well defined. This article will describe recent data that shows long term effects of maternal deficiency on offspring memory function. On the other side, maternal over supplementation of folic acid has recently been reported to have negative effects on neurodevelopment. Over supplementation is defined as ingesting over 1 mg of folic acid daily. Using a mouse model, we investigated the long-term effects of maternal deficiencies of folic acid on offspring memory function. Female mice were put on a diet deficient in folic acid prior to pregnancy (Jadavji et al., 2015). The impact of maternal deficiency on offspring memory function was evaluated. The offspring were ~3 weeks which is equivalent to young adults. Our research findings suggest that offspring from moms with a folic acid deficiency had impaired short-term visual memory. This may be a result of increased cell death and reduced cell proliferation within the hippocampus, a structure in the brain that is involved in memory. Being folic acid deficient is not recommended for women of child bearing age, not only to avoid NTD, but also for neurodevelopment after birth. Recently, there have been concerns about over supplementation of folic acid in countries like Canada where mandatory folic acid fortification laws are in place and supplement use is high (Patel and Sobczynska-Malefora, 2017). In epidemiological studies, too much folic acid has been associated with increased risk of cancer (Boyles et al., 2016). Interestingly, too much maternal folic acid intake has been associated with autism spectrum disorder (Beard et al., 2011), but the data is not clear as other studies have reported the protective effects (Wang et al., 2017). Furthermore, too much maternal folic acid has been reported to impair other neurodevelopmental aspects of the brain and behavior in offspring (Roth et al., 2011). We recently published a study (Bahous et al., 2017) investigating whether too much maternal folic acid is associated with changes in the neurodevelopment of offspring. Using a mouse model of maternal over supplementation of folic acid we report that male offspring from mothers that were fed high levels of folic acid had impaired memory and brain development. The amount of folic acid in the diet of mothers was 20mg/kg to model over supplementation in humans. Mothers were supplemented for 6 weeks prior to pregnancy and throughout lactation. Once we weaned the pups from mothers they were maintained on supplemented diet until we collected experimental data. We assessed short-term memory of mice using a test called the novel object recognition, animals from mothers with too much folic acid did not remember seeing a familiar object as well as control animals did. Furthermore, they had reduced levels of a neurotransmitter that is important in learning and memory called acetylcholine. The pups from mothers over supplemented folic acid mothers had altered development of the cortex. This means that part of their brain did not follow normal development patterns. Interestingly the offspring from maternally over supplemented folic acid mother showed a similar phenotype to that of mice with a genetic deficiency in folic acid metabolism (Jadavji et al., 2012). These are some of the first results showing how maternal over supplementation with folic acid may affect early neurodevelopment. More studies are required to further dissect the mechanisms as well as determine if the benefits continue into adulthood. As someone wise once said, everything in moderation. I originally wrote this post for fem STEM in February 2018.
I am a neuroscientist by training; I started working in a university lab letting during the first year of my undergraduate degree in 2002. This year, 2018, I am starting my 6th year of postdoctoral training. Part of my postdoc training was completed in Berlin, Germany at the Charité Medical University. It was a dream of mine to live in Europe and I enjoyed it a lot. During my time in Germany, I travelled to many other countries and experienced different cultures. I also formed a number of fruitful scientific collaborations. In 2015, I returned home to Canada and continued my scientific training. My research program focuses on nutritional neuroscience, with a specific focus on folic acid, a B-vitamin, and neurodegeneration. I work in a mouse model. I study vascular cognitive impairment and stroke, as well as Parkinson’s disease. Some of my research tools include behavioral testing, in vivoimaging, using MRI, primary cell cultures and biochemistry assays, such as Western Blot. When I completed my PhD in 2012, I was very eager to get going on my postdoctoral research and move into an independent position, at the time I did not realize the importance of postdoctoral training. When I defended my doctoral thesis in late 2012, I felt that I was on top of the world and that I could do anything, like run my own lab. Little did I know that was not the case, there is a significant amount of training required when moving from doctoral work to leading a research group. While I was completing my first postdoc at the Charité Medical University in Berlin, I had the opportunity to mentor and supervise a 4 MSc. students, develop a course for graduate students, writing grants, and drive my own research project. At first, I felt daunted by all these tasks, but it was also very exciting and made me work harder. The experience I had was priceless; I learned a lot that I would not have if I had not taken on these additional responsibilities. My time at the Charité helped me transition from a student to supervisor and mentor. This was further extended when I moved back to Canada and into my second postdoc position at Carleton University. I have been driving my research program since beginning my postdoc in 2013. So far in my training I have mentored and supervised over 33 trainees, including high school, undergraduate, and graduate students. I have published 16 peer reviewed articles since beginning my postdoc training in 2013. These experiences have helped me learn techniques, strategies, and important lessons I think I need to know in order to lead a team of researchers in the future. I have not taken the traditional road to postdoctoral training. This means that I did not go into someone’s laboratory and do experiments to help move their research program forward. What I did do was obtain my own funding and drive my own research project. In my last two years of PhD training I did a lot of research to find potential labs and wrote a number of fellowship applications to fund my postdoctoral training. I knew exactly what I wanted to do in terms of research area and so I ran with it. I was successful in obtaining funding for five years from the provincial and federal Canadian government. Along the way I also got some small pots of money to help with meeting travel. I was successful in obtaining operating grant money twice which was a great to help with the costs of running experiments. I have faced a lot of road blocks and rejection along the way, and I still do. But persistence and a strong will has helped me stay on path for a career in STEM. I think I have learned a number of important lessons from my scientific training and the two top things I try and pass on are; one take a break from time to time, don’t burn yourself out. Take some time away from work and come back refreshed, you will work better. Two, rejection is important. You can’t be good at everything. Failing is important, you learn how to pick yourself up and get going again, these lessons have been priceless. Pursuing my own research program has also been a lonely path; I have been surrounded by people in the lab but there are not very many people in my current surroundings that are experts in my field. Although a challenge, I have embraced it and made a number of collaborations with others in and outside of the field. I have also expanded my research by working with others different areas, it has been a good challenge to embrace. I think that postdoctoral training is very important for scientists in STEM. It is a difficult time because the future is not certain, job security is scarce. But when done correctly it can give an individual the experience and confidence that they require to run their own laboratory or to go down their own path. If you love what you do, go for it! I wrote this post for the website called Women in Science in 2017.
I am a female Canadian Neuroscientist interested in how nutrition, specifically B-vitamins and age impact brain function. The B-vitamin I work closely with is called folic acid, it is well known for its role during early neurodevelopment. Specifically, for the closure of the neural tube in utero. The neural tube in embryos is the first step to forming the brain and spinal cord. If the neural tube does not close, it leads to the development of neural tube defects (NTDs) in babies, such as spina bifida. To prevent the NTDs, mandatory folic acid fortification laws were put into place in 1998 in the US and Canada, as well as other countries. Since 1998 there has been a reduction in the number of NTDs in both Canada and the US. Recently, there have been concerns about over supplementation of folic acid in countries like Canada where mandatory folic acid fortification laws are in place and supplement use is high (Patel and Sobczynska-Malefora, 2017). In epidemiological studies, too much folic acid has been associated with increased risk of cancer (Boyles et al., 2016). Interestingly, too much maternal folic acid intake has been associated with autism spectrum disorder (Beard et al., 2011), but the data is not clear as other studies have reported the protective effects (Wang et al., 2017). Furthermore, too much maternal folic acid has been reported to impair other neurodevelopmental aspects of the brain and behavior in offspring (Roth et al., 2011). We recently published a study (Bahous et al., 2017) investigating whether too much maternal folic acid is associated with changes in the neurodevelopment of offspring. Using a mouse model of maternal over supplementation of folic acid we report that male offspring from mothers that were fed high levels of folic acid had impaired memory and brain development. The amount of folic acid in the diet of mothers was minimal (5mg/kg of folic acid) and comparable to human supplementation. Mothers were supplemented for 6 weeks prior to pregnancy and throughout lactation. Once we weaned the pups from mothers they were maintained on supplemented diet until we collected experimental data. We assessed short-term memory of mice using a test called the novel object recognition, animals from mothers with too much folic acid did not remember seeing a familiar object as well as control animals did. Furthermore, they had reduced levels of a neurotransmitter that is important in learning and memory called acetylcholine. The pups from mothers over supplemented folic acid mothers had altered development of the cortex. Interestingly the offspring from maternally over supplemented folic acid mother showed a similar phenotype to that of mice with in born error of metabolism (Jadavji et al., 2012). These are some of the first results showing how maternal over supplementation with folic acid may affect early neurodevelopment. More studies are required to further dissect the mechanisms as well as determine if the benefits continue into adulthood. As someone wise once said, everything in moderation 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 Carleton University 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.
Demographics:
Work: 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. Outside Life: 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. Big Picture: 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. Fun Questions: 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. |
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