This Minority Career Development Award is focused on establishing the relationship between air pollutants and brain neurodevelopmental and neurodegenerative diseases. This will be accomplished in an institutional environment that is highly supportive, with multidisciplinary expertise, state-of-the art equipment and facilities that is deeply committed to a successful mentoring experience. The research plan is based on the hypothesis that air pollutants produce respiratory tract inflammation, followed by the production of mediators of inflammation capable of reaching the brain (including the fetal brain). In addition, pollutants directly enter the brain through neural pathways from the olfactory epithelium. The 5-year research plan is divided in 3 stages: Stage I. Oxidative DNA damage in brain and nasal respiratory and olfactory tissues of healthy canines exposed to urban pollution. The innovation of this stage is to study naturally exposed animals, apply a spectrum of highly sensitive assays to measure oxidative DNA damage as a biomarker so that the association between persistent oxidative stress and neurodegenerative diseases can be identified. By selecting biomarkers of direct radical and lipid peroxidation-induced DNA damage it will be possible to determine the pathways of oxidative damage in pollution-exposed brains. These results will be compared and contrasted with alterations in neuropathology and immunohistochemistry. Stage II. DNA oxidative damage and mediators of inflammation in brains of children and adults exposed to urban pollution. The main objective of this stage is to determine if a sustained inflammatory process elicited by chronic exposure to pollutants causes brain oxidative DNA damage and/or alterations in mediators of inflammation in cognitively and neurologically intact subjects residents in highly polluted cities, and if there is a neuropathology counterpart. Stage III. DNA damage and mediators of inflammation in the developing dog brain exposed to air pollutants. This stage addresses the crux of this proposal: Effects of pollution upon the exposed fetus. The Award will give me the opportunity to build new skills in 4 areas: Molecular Biology, DNA Damage, Developmental / Neurodegenerative Neuropathology, and to gain experience in grantsmanship. ? ?
