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2013 Grants - Axelsen
Maternally Determined Predisposition to Oxidative Stress
Paul H. Axelsen, M.D.
University of Pennsylvania
2013 Investigator-Initiated Research Grant
Oxidation, the process by which oxygen is utilized by cells, is a naturally occurring process that can also damage proteins and cells, including nerve cells in the brain. The body employs numerous systems to limit oxidation, but damage still occurs. An increased propensity for oxidative damage in living tissues is known as oxidative stress. Oxidative stress has been implicated in brain cell damage in Alzheimer's disease.
Brain development in very young animals is influenced by oxidative stress, and one source of oxidative stress is the abnormal metabolism of polyunsaturated fatty acids (PUFAs). Paul H. Axelsen, M.D. and colleagues have suggested that oxidated PUFAs in the brain may contribute to nerve cell toxicity and Alzheimer's disease.
Dr. Axelsen and colleagues have proposed to study how exposure to PUFAs before birth affects the brain's ability to resist oxidative stress later in life. Using mice that have been genetically altered to have an Alzheimer's-like condition, the researchers will expose pregnant mice to various diets containing different levels of PUFAs. They will then study the offspring to determine their susceptibility to oxidative damage in the brain, and to the development of Alzheimer's-like brain changes. These studies will help to clarify the role of oxidative stress and maternal diet in the susceptibility to Alzheimer's disease.