How Does Nutrition Impact Stroke Outcome? Understanding the Role of One-carbon Metabolism in Ischemic Stroke

Dr. Jadavji is a postdoctoral fellow and instructor at Carleton University and the University of Ottawa. Since beginning her scientific training in 2002, Dr. Jadavji has published 26 peer reviewed articles. Her research findings have been published in Human Molecular Genetics, Neurobiology of Disease, Nutrition Reviews, and the Journal of Neuroscience. During her postdoctoral training she has obtained $324,000 CDN in research funding, including 2 operating grants. Additionally, Dr. Jadavji has developed courses at the undergraduate and graduate level, as well as co-supervised 37 trainees. Her research focuses on understanding the mechanisms through which dietary and genetic deficiencies in one carbon metabolism, affect neurological function over the lifespan. One of the objectives of Dr. Jadavji’s research program is to investigate the mechanisms through which one-carbon metabolism impacts stroke onset and progression using a mouse model. Stroke is a leading cause of disability and death world-wide. Increased levels of homocysteine have been associated with risk for stroke. Metheylenetetrahydrofolate reductase (MTHFR) is an enzyme that links folate and homocysteine metabolism. In all tissues, including in the brain, MTHFR catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (5-methylTHF). The methyl group from 5-methylTHF is a substrate in the vitamin-B12-dependent methylation of homocysteine to form methionine by methionine synthase. A polymorphism in MTHFR (677CT), identified in 5-15% of North American and European populations, may increase risk of stroke. Dr. Jadavji’s research findings demonstrate that a genetic deficiency in MTHFR results in increased vulnerability of primary neurons and astrocytes to damage through reduced cell viability. In vivo, aged Mthfr+/- mice show impairment in skilled motor function after ischemic damage. The damaged brain of Mthfr+/- mice shows increased apoptosis and reduced neuronal survival. Interestingly, supplementation of one-carbon metabolism after ischemic damage in wild-type mice results in reduced functional impairment. Supplementation also increases neuronal proliferation, plasticity, and anti-oxidant activity within the damaged brain.

One carbon metabolism plays a role in the onset and progression of ischemic stroke, as shown by Dr. Jadavji’s research findings. These results highlight the importance of incorporating nutrition into lifestyle changes for high risk individuals as well as stroke affected patients.

Dr. Jadavji is a candidate for the position of Assistant Professor in Nutritional Biochemistry