Long-term exposure to black carbon, cognition and single nucleotide polymorphisms in microRNA processing genes in older men

Colicino, Elena; Giuliano, Giulia; Power, Melinda C.; Lepeule, Johanna; Wilker, Elissa H.; Vokonas, Pantel; Brennan, Kasey; Fossati, Serena; Hoxha, Mirjam; Spiro, Avron; Weisskopf, Marc G.; Schwartz, Joel; Baccarelli, Andrea A.

doi:10.1016/j.envint.2015.12.014

Cited by 23 publications

(12 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, several miRNAs target BACE1, including miR-9, miR-29, miR-107, miR-186, miR-188, miR-298, and miR-328, some of which are closely related to synaptic and cognitive function [ 40 , 41 ]. A recent study reported that long-term exposure to black carbon was linked to cognitive status due to influences on miRNA expression [ 79 ]. However, little is known regarding whether miRNAs aggravate synaptic and cognitive dysfunction by elevating the expression of BACE1 following PM 2.5 exposure.…”

Section: Discussionmentioning

confidence: 99%

NF-κB-regulated microRNA-574-5p underlies synaptic and cognitive impairment in response to atmospheric PM2.5 aspiration

Gao

et al. 2017

Part Fibre Toxicol

117

View full text Add to dashboard Cite

BackgroundPM2.5 (particulate matter ≤ 2.5 μm) is one of the leading environmental risk factors for the global burden of disease. Whereas increasing evidence has linked the adverse roles of PM2.5 with cardiovascular and respiratory diseases, limited but growing emerging evidence suggests that PM2.5 exposure can affect the nervous system, causing neuroinflammation, synaptic dysfunction and cognitive deterioration. However, the molecular mechanisms underlying the synaptic and cognitive deficits elicited by PM2.5 exposure are largely unknown.MethodsC57BL/6 mice received oropharyngeal aspiration of PM2.5 (1 and 5 mg/kg bw) every other day for 4 weeks. The mice were also stereotaxically injected with β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE1) shRNA or LV-miR-574-5p lentiviral constructs in the absence or presence of PM2.5 aspiration at 5 mg/kg bw every other day for 4 weeks. Spatial learning and memory were assessed with the Morris water maze test, and synaptic function integrity was evaluated with electrophysiological recordings of long-term potentiation (LTP) and immunoblot analyses of glutamate receptor subunit expression. The expression of α-secretase (ADAM10), BACE1, and γ-secretase (nicastrin) and the synthesis and accumulation of amyloid β (Aβ) were measured by immunoblot and enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) expression was screened with a microRNA microarray analysis and confirmed by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Dual-luciferase reporter gene and chromatin immunoprecipitation (ChIP) analyses were used to detect the binding of miR-574-5p in the 3’UTR of BACE1 and NF-κB p65 in the promoter of miR-574-5p, respectively.ResultsPM2.5 aspiration caused neuroinflammation and deteriorated synaptic function integrity and spatial learning and memory, and the effects were associated with the induction of BACE1. The action was mediated by NF-κB p65-regulated downregulation of miR-574-5p, which targets BACE1. Overexpression of miR-574-5p in the hippocampal region decreased BACE1 expression, restored synaptic function, and improved spatial memory and learning following PM2.5 exposure.ConclusionsTaken together, our findings reveal a novel molecular mechanism underlying impaired synaptic and cognitive function following exposure to PM2.5, suggesting that miR-574-5p is a potential intervention target for the prevention and treatment of PM2.5-induced neurological disorders.Electronic supplementary materialThe online version of this article (10.1186/s12989-017-0215-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

NF-κB-regulated microRNA-574-5p underlies synaptic and cognitive impairment in response to atmospheric PM2.5 aspiration

Gao

et al. 2017

Part Fibre Toxicol

117

View full text Add to dashboard Cite

show abstract

“…We selected PM 2.5 and BC as our ambient particle exposures because of their global pervasiveness [1] in addition to their status as the leading ambient particles with well-documented relationships with both DNA methylation [53–55] and adverse health outcomes [56–59]. …”

Section: Methodsmentioning

confidence: 99%

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

et al. 2016

Self Cite

View full text Add to dashboard Cite

BackgroundAmbient particles have been shown to exacerbate measures of biological aging; yet, no studies have examined their relationships with DNA methylation age (DNAm-age), an epigenome-wide DNA methylation based predictor of chronological age.ObjectiveWe examined the relationship of DNAm-age with fine particulate matter (PM2.5), a measure of total inhalable particle mass, and black carbon (BC), a measure of particles from vehicular traffic.MethodsWe used validated spatiotemporal models to generate 1-year PM2.5 and BC exposure levels at the addresses of 589 older men participating in the VA Normative Aging Study with 1–3 visits between 2000 and 2011 (n = 1032 observations). Blood DNAm-age was calculated using 353 CpG sites from the Illumina HumanMethylation450 BeadChip. We estimated associations of PM2.5 and BC with DNAm-age using linear mixed effects models adjusted for age, lifestyle/environmental factors, and aging-related diseases.ResultsAfter adjusting for covariates, a 1-µg/m3 increase in PM2.5 (95% CI: 0.30, 0.75, P<0.0001) was significantly associated with a 0.52-year increase in DNAm-age. Adjusted BC models showed similar patterns of association (β = 3.02, 95% CI: 0.48, 5.57, P = 0.02). Only PM2.5 (β = 0.54, 95% CI: 0.24, 0.84, P = 0.0004) remained significantly associated with DNAm-age in two-particle models. Methylation levels from 20 of the 353 CpGs contributing to DNAm-age were significantly associated with PM2.5 levels in our two-particle models. Several of these CpGs mapped to genes implicated in lung pathologies including LZTFL1, PDLIM5, and ATPAF1.ConclusionOur results support an association of long-termambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes.

show abstract

“…Regarding the potential role of miRNAs in the effects of PM on CNS function, long-term exposure to BC was shown to be associated with cognitive impairment in older men, which was also associated with SNPs in miRNA processing genes (27).…”

Section: Mirnas and Heavy Metalsmentioning

confidence: 99%

The Role of MicroRNAs in Environmental Risk Factors, Noise-Induced Hearing Loss, and Mental Stress

Miguel

Cui

Daimiel

et al. 2018

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

Long-term exposure to black carbon, cognition and single nucleotide polymorphisms in microRNA processing genes in older men

Cited by 23 publications

References 49 publications

NF-κB-regulated microRNA-574-5p underlies synaptic and cognitive impairment in response to atmospheric PM2.5 aspiration

NF-κB-regulated microRNA-574-5p underlies synaptic and cognitive impairment in response to atmospheric PM2.5 aspiration

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

The Role of MicroRNAs in Environmental Risk Factors, Noise-Induced Hearing Loss, and Mental Stress

Contact Info

Product

Resources

About