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

Calderón‐Garcidueñas, Lilian; Herrera-Soto, Andrea; Jury, Nur; Maher, Barbara A.; González-Maciel, Angélica; Reynoso-Robles, Rafael; Ruiz-Rudolph, Pablo; Zundert, Brigitte van; Varela-Nallar, Lorena

doi:10.1016/j.envres.2020.109226

Cited by 70 publications

(35 citation statements)

References 59 publications

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“…These experimental results coincide with (i) the detection of airNPs in postmortem brains of animals and humans with chronic, long-term exposure to air pollution in metropolitan areas [ 6 ], (ii) the detection of airNPs and AD pathology in brains of laboratory mice exposed to traffic-related nanomaterials [ 13 ] and (iii) epidemiological data that identifies the proximity of a residence near busy roads as a risk factor for the development of the neurodegenerative disease AD [ 8 ].…”

Section: Conclusion and Future Perspectivessupporting

confidence: 69%

“…Notably, previous studies identified the key exposure zone of traffic-related nanoparticles within 500 m and critically within 50 m from the traffic route [ 9 , 10 ]. The inhalation of air pollution and diesel exhaust was shown to induce inflammatory changes as well as hallmarks of AD, including amyloid formation [ 11 , 12 , 13 ] ( 1.2 ). A recent review summarized the results from epidemiological studies indicating that exposure to air pollution can have adverse effects on cognitive decline and impairment [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Of particular concern is the association of air pollution, combustion- and friction-derived NPs in young populations (i.e., children and young adults living in major cities, [ 6 ]). Rodent animal models of urban nanoparticulate air pollution show the consistent induction of inflammatory responses in major brain regions, increased DNA damage in cell nuclei of central neurons, and increased levels of AD-related tau phosphorylation [ 11 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Airborne Nanoparticles on the Nervous System: Amyloid Protein Aggregation, Neurodegeneration and Neurodegenerative Diseases

Mikecz

Schikowski

2020

Nanomaterials

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How the environment contributes to neurodegenerative diseases such as Alzheimer’s is not well understood. In recent years, science has found augmenting evidence that nano-sized particles generated by transport (e.g., fuel combustion, tire wear and brake wear) may promote Alzheimer’s disease (AD). Individuals residing close to busy roads are at higher risk of developing AD, and nanomaterials that are specifically generated by traffic-related processes have been detected in human brains. Since AD represents a neurodegenerative disease characterized by amyloid protein aggregation, this review summarizes our current knowledge on the amyloid-generating propensity of traffic-related nanomaterials. Certain nanoparticles induce the amyloid aggregation of otherwise soluble proteins in in vitro laboratory settings, cultured neuronal cells and vertebrate or invertebrate animal models. We discuss the challenges for future studies, namely, strategies to connect the wet laboratory with the epidemiological data in order to elucidate the molecular bio-interactions of airborne nanomaterials and their effects on human health.

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Section: Conclusion and Future Perspectivessupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Airborne Nanoparticles on the Nervous System: Amyloid Protein Aggregation, Neurodegeneration and Neurodegenerative Diseases

Mikecz

Schikowski

2020

Nanomaterials

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“…However, our study differed significantly from prior research with respect to the duration of exposure (up to 14 months in our study vs. several weeks or months in prior research), as well as the composition and concentration of TRAP to which animals were exposed. With regard to the latter, with the exception of one study that examined the effects of ambient air pollution in Santiago, Chile ( Calderón-Garcidueñas et al. 2020 ), most preclinical research has focused on neurological effects of isolated fractions of TRAP.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Chronic Exposure to Ambient Traffic-Related Air Pollution on Alzheimer’s Disease Phenotypes in Wildtype and Genetically Predisposed Male and Female Rats

Patten

Valenzuela

Wallis

et al. 2021

Environ Health Perspect

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Background: Epidemiological data link traffic-related air pollution (TRAP) to increased risk of Alzheimer’s disease (AD). Preclinical data corroborating this association are largely from studies of male animals exposed acutely or subchronically to high levels of isolated fractions of TRAP. What remains unclear is whether chronic exposure to ambient TRAP modifies AD risk and the influence of sex on this interaction. Objectives: This study sought to assess effects of chronic exposure to ambient TRAP on the time to onset and severity of AD phenotypes in a preclinical model and to determine whether sex or genetic susceptibility influences outcomes. Methods: Male and female TgF344-AD rats that express human AD risk genes and wildtype littermates were housed in a vivarium adjacent to a heavily trafficked tunnel in Northern California and exposed for up to 14 months to filtered air (FA) or TRAP drawn from the tunnel and delivered to animals unchanged in real time. Refractive particles in the brain and AD phenotypes were quantified in 3-, 6-, 10-, and 15-month-old animals using hyperspectral imaging, behavioral testing, and neuropathologic measures. Results: Particulate matter (PM) concentrations in TRAP exposure chambers fluctuated with traffic flow but remained below 24-h PM with aerodynamic diameter less than or equal to 2.5 micrometers ( ) U.S. National Ambient Air Quality Standards limits. Ultrafine PM was a predominant component of TRAP. Nano-sized refractive particles were detected in the hippocampus of TRAP animals. TRAP-exposed animals had more amyloid plaque deposition, higher hyperphosphorylated tau levels, more neuronal cell loss, and greater cognitive deficits in an age-, genotype-, and sex-dependent manner. TRAP-exposed animals also had more microglial cell activation, but not astrogliosis. Discussion: These data demonstrate that chronic exposure to ambient TRAP promoted AD phenotypes in wildtype and genetically susceptible rats. TRAP effects varied according to age, sex, and genotype, suggesting that AD progression depends on complex interactions between environment and genetics. These findings suggest current regulations are insufficient to protect the aging brain. https://doi.org/10.1289/EHP8905

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“…Another study conducted in human blood samples demonstrated that environmental pollutants such as fine particulate matter (PM2.5) cause global changes in H3K27 acetylation, notably in genes involved in immune cell activation (15). Besides, exposure to particulate matter, urban air pollution also leads to reduction in repressive H3K9me3 and H3K9me2 marks in the postmortem human brain (16).…”

Section: Introductionmentioning

confidence: 99%

In utero exposure to chlordecone affects histone modifications and activates LINE-1 in cord blood

et al. 2021

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Environmental factors can induce detrimental consequences into adulthood life. In this study, we examined the epigenetic effects induced by in utero chlordecone (CD) exposure on human male cord blood as well as in blood-derived Ke-37 cell line. Genome-wide analysis of histone H3K4me3 distribution revealed that genes related to chromosome segregation, chromatin organization, and cell cycle have altered occupancy in their promoters. The affected regions were enriched in ESR1, SP family, and IKZF1 binding motifs. We also observed a global reduction in H3K9me3, markedly in repeated sequences of the genome. Decrease in H3K9me3 after CD exposure correlates with decreased methylation in LINE-1 promoters and telomere length extension. These observations on human cord blood were assessed in the Ke-37 human cell line. H3K4me3 and the expression of genes related to immune response, DNA repair, and chromatin organization, which were affected in human cord blood were also altered in CD-exposed Ke-37 cells. Our data suggest that developmental exposure to CD leads to profound changes in histone modification patterns and affects the processes controlled by them in human cord blood.

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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

Cited by 70 publications

References 59 publications

Effects of Airborne Nanoparticles on the Nervous System: Amyloid Protein Aggregation, Neurodegeneration and Neurodegenerative Diseases

Effects of Airborne Nanoparticles on the Nervous System: Amyloid Protein Aggregation, Neurodegeneration and Neurodegenerative Diseases

The Effects of Chronic Exposure to Ambient Traffic-Related Air Pollution on Alzheimer’s Disease Phenotypes in Wildtype and Genetically Predisposed Male and Female Rats

In utero exposure to chlordecone affects histone modifications and activates LINE-1 in cord blood

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