title: DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration.
abstract: Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer's-type pathology in dogs chronically exposed to air pollutants. Respiratory tract inflammation and deteriorating olfactory and respiratory barriers may play a role in the observed neuropathology. These data suggest that Alzheimer's disease may be the sequela of air pollutant exposures and the resulting systemic inflammation.
authors.affiliation: Environmental Pathology Program, University of North Carolina at Chapel Hill, North Carolina 27599-7310, USA. liliancalderon888@hotmail.com
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.forename: Robert R
authors.initials: RR
authors.lastname: Maronpot
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardon
authors.forename: Carlos
authors.initials: C
authors.lastname: Henríquez-Roldán
authors.forename: Robert
authors.initials: R
authors.lastname: Schoonhoven
authors.forename: Hilda
authors.initials: H
authors.lastname: Acuña-Ayala
authors.forename: Anna
authors.initials: A
authors.lastname: Villarreal-Calderón
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Reshan
authors.initials: R
authors.lastname: Fernando
authors.forename: William
authors.initials: W
authors.lastname: Reed
authors.forename: Biagio
authors.initials: B
authors.lastname: Azzarelli
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
mesh_terms: D017677:Age Distribution; D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D002908:Chronic Disease; D004249:DNA Damage; D004285:Dogs; D004660:Encephalitis / Q000139:chemically induced / Q000209:etiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D008800:Mexico; D008954:Models, Biological; D009297:Nasal Mucosa / Q000187:drug effects*; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects; D009830:Olfactory Bulb / Q000187:drug effects
chemical_list: D000393:Air Pollutants