Browsing by Author "Reynoso-Robles, Rafael"

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    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
    (2020) Calderon-Garciduenas, Lilian; Herrera-Soto, Andrea; Jury, Nur; Maher, Barbara A.; Gonzalez-Maciel, Angelica; Reynoso-Robles, Rafael; Ruiz-Rudolph, Pablo; van Zundert, Brigitte; Varela-Nallar, Lorena
    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.