TY - JOUR
T1 - 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
AU - Calderón-Garcidueñas, Lilian
AU - Herrera-Soto, Andrea
AU - Jury, Nur
AU - Maher, Barbara A.
AU - González-Maciel, Angélica
AU - Reynoso-Robles, Rafael
AU - Ruiz-Rudolph, Pablo
AU - van Zundert, Brigitte
AU - Varela-Nallar, Lorena
N1 - Funding Information:
This work was supported by grants from FONDECYT N?1190461 (LVN), FONDECYT N? 1181645 (BvZ), Nucleo UNAB N? DI-4-17/N (LVN and BvZ), CARE-UC AFB 170005 (BvZ), CONICYT 201161486 (NJ) and Mexico SEP-CONACYT # 255956 (LCG). All authors declare non-financial competing interests.
Funding Information:
This work was supported by grants from FONDECYT N° 1190461 (LVN), FONDECYT Nº 1181645 (BvZ), Nucleo UNAB Nº DI-4-17/N (LVN and BvZ), CARE-UC AFB 170005 (BvZ), CONICYT 201161486 (NJ) and Mexico SEP-CONACYT # 255956 (LCG). All authors declare non-financial competing interests.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
N2 - 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 γ-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 γ-H2A.X staining were present in MMC urbanites, who also displayed the presence of hyperphosphorylated tau and amyloid-β (Aβ) 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 γ-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.
AB - 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 γ-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 γ-H2A.X staining were present in MMC urbanites, who also displayed the presence of hyperphosphorylated tau and amyloid-β (Aβ) 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 γ-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.
KW - Alzheimer's disease
KW - Combustion- and friction-derived nanoparticles
KW - Epigenetics
KW - Frontal cortex
KW - Particulate air pollution
UR - http://www.scopus.com/inward/record.url?scp=85079010431&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2020.109226
DO - 10.1016/j.envres.2020.109226
M3 - Article
C2 - 32045727
AN - SCOPUS:85079010431
SN - 0013-9351
VL - 183
JO - Environmental Research
JF - Environmental Research
M1 - 109226
ER -