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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01NS046410-03
Application #
7115309
Study Section
NST-2 Subcommittee (NST)
Program Officer
Jett, David A
Project Start
2004-09-15
Project End
2009-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
3
Fiscal Year
2006
Total Cost
$164,298
Indirect Cost
Name
University of Montana
Department
Other Health Professions
Type
Schools of Pharmacy
DUNS #
010379790
City
Missoula
State
MT
Country
United States
Zip Code
59812
Calderón-Garcidueñas, Lilian; Serrano-Sierra, Alejandro; Torres-Jardón, Ricardo et al. (2013) The impact of environmental metals in young urbanites' brains. Exp Toxicol Pathol 65:503-11
Villarreal-Calderon, Rodolfo; Reed, William; Palacios-Moreno, Juan et al. (2012) Urban air pollution produces up-regulation of myocardial inflammatory genes and dark chocolate provides cardioprotection. Exp Toxicol Pathol 64:297-306
Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Henríquez-Roldán, Carlos et al. (2010) Urban air pollution: influences on olfactory function and pathology in exposed children and young adults. Exp Toxicol Pathol 62:91-102
Calderon-Garciduenas, Lilian; Macias-Parra, Mercedes; Hoffmann, Hans J et al. (2009) Immunotoxicity and environment: immunodysregulation and systemic inflammation in children. Toxicol Pathol 37:161-9
Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Gómez-Garza, Gilberto et al. (2009) Effects of a cyclooxygenase-2 preferential inhibitor in young healthy dogs exposed to air pollution: a pilot study. Toxicol Pathol 37:644-60
Calderon-Garciduenas, Lilian; Solt, Anna C; Henriquez-Roldan, Carlos et al. (2008) Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and youn Toxicol Pathol 36:289-310
Calderon-Garciduenas, L; Villarreal-Calderon, R; Valencia-Salazar, G et al. (2008) Systemic inflammation, endothelial dysfunction, and activation in clinically healthy children exposed to air pollutants. Inhal Toxicol 20:499-506
Calderon-Garciduenas, Lilian; Franco-Lira, Maricela; Torres-Jardon, Ricardo et al. (2007) Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology. Toxicol Pathol 35:154-62
Calderon-Garciduenas, Lilian; Vincent, Renaud; Mora-Tiscareno, Antonieta et al. (2007) Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution. Environ Health Perspect 115:1248-53