Reduced repressive epigenetic marks, increased DNA damage and Alzheimer's disease hallmarks in the brain of humans and mice exposed to particulate urban air pollution
Author
dc.contributor.author
Calderón Garcidueñas, Lilian
Author
dc.contributor.author
Herrera Soto, Andrea
Author
dc.contributor.author
Jury, Nur
Author
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Maher, Bárbara
Author
dc.contributor.author
González Maciel, Angélica
Author
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Reynoso Robles, Rafael
Author
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Ruiz Rudolph, Pablo
Author
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van Zundert, Brigitte
Author
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Varela Nallar, Lorena
Admission date
dc.date.accessioned
2020-05-28T22:43:33Z
Available date
dc.date.available
2020-05-28T22:43:33Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Environmental Research 183 (2020) 109226
es_ES
Identifier
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10.1016/j.envres.2020.109226
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/175078
Abstract
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Exposure to air pollutants is associated with an increased risk of developing Alzheimer's disease (AD). AD pathological hallmarks and cognitive deficits are documented in children and young adults in polluted cities (e.g. Metropolitan Mexico City, MMC). Iron-rich combustion- and friction-derived nanoparticles (CFDNPs) that are abundantly present in airborne particulate matter pollution have been detected in abundance in the brains of young urbanites. Epigenetic gene regulation has emerged as a candidate mechanism linking exposure to air pollution and brain diseases. A global decrease of the repressive histone post-translational modifications (HPTMs) H3K9me2 and H3K9me3 (H3K9me2/me3) has been described both in AD patients and animal models. Here, we evaluated nuclear levels of H3K9me2/me3 and the DNA double-strand-break marker gamma-H2AX by immunostaining in post-mortem prefrontal white matter samples from 23 young adults (age 29 +/- 6 years) who resided in MMC (n = 13) versus low-pollution areas (n = 10). Lower H3K9me2/me3 and higher gamma-H2A.X staining were present in MMC urbanites, who also displayed the presence of hyperphosphorylated tau and amyloid-beta (A beta) plaques. Transmission electron microscopy revealed abundant CFDNPs in neuronal, glial and endothelial nuclei in MMC residents' frontal samples. In addition, mice exposed to particulate air pollution (for 7 months) in urban Santiago (Chile) displayed similar brain impacts; reduced H3K9me2/me3 and increased gamma-H2A.X staining, together with increased levels of AD-related tau phosphorylation. Together, these findings suggest that particulate air pollution, including metal-rich CFDNPs, impairs brain chromatin silencing and reduces DNA integrity, increasing the risk of developing AD in young individuals exposed to high levels of particulate air pollution.
es_ES
Patrocinador
dc.description.sponsorship
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT
1190461
1181645
Nucleo UNAB
DI-4-17/N
CARE-UC
AFB 170005
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
201161486
Mexico SEP-CONACYT
255956
Reduced repressive epigenetic marks, increased DNA damage and Alzheimer's disease hallmarks in the brain of humans and mice exposed to particulate urban air pollution