Brain Inflammation and Alzheimer's-Like Pathology in Individuals Exposed to Severe Air Pollution

Toxicologic Pathology - Tập 32 Số 6 - Trang 650-658 - 2004
Lilian Calderón‐Garcidueñas1, William Reed2, Robert R. Maronpot3, Carlos Henríquez-Roldán4, Ricardo Delgado‐Chávez5, Ana Laura Calderón‐Garcidueñas6, Irma Dragustinovis7, Maricela Franco-Lira8, Mariana Aragón-Flores9, Anna C. Solt10, Michael K. Altenburg11, Ricardo Torres‐Jardón12, James A. Swenberg13
1Instituto Nacional de Pediatría, Mexico City 14410, Mexico, Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599-7525, USA
2Department of Pediatrics and Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, 27599-7310, USA
3National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA
4Departamento de Estadística, Universidad de Valparaíso, Chile
5Pathology Department, Instituto Nacional de Cancerología, Mexico City, Mexico
6Hospital de Especialidades No. 25, and Centro de Investigación Biomédica del Noreste CIBIN, IMSS, Monterrey, NL, Mexico
7Hospital de Especialidades No. 25, IMSS, Monterrey, NL, Mexico
8Escuela Médico Militar, Universidad del Ejército y Fuerza Aérea, Mexico City, Mexico
9Departamento de Patología, Hospital Central Militar, Mexico City, Mexico
10Facultad de Medicina, NUCE, Universidad Nacional Autónoma de México, Mexico City, Mexico
11Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599-7525, USA
12Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City, Mexico
13Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599-7525, USA, Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599-7431, USA,

Tóm tắt

Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of β-amyloid (A β42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor- κB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of A β42 compared to residents in low air pollution cities. Increased COX2 expression and A β42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe airpollution is associated with brain inflammation and A β 42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

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