title: The impact of environmental metals in young urbanites' brains.
abstract: Air pollution exposures are linked to cognitive and olfaction deficits, oxidative stress, neuroinflammation and neurodegeneration including frontal hyperphosphorylated tau and diffuse amyloid plaques in Mexico City children and young adults. Mexico City residents are chronically exposed to fine particulate matter (PM(2.5)) concentrations (containing toxic combustion and industrial metals) above the annual standard (15 μg/m(3)) and to contaminated water and soil. Here, we sought to address the brain-region-specific effects of metals and key neuroinflammatory and DNA repair responses in two air pollution targets: frontal lobe and olfactory bulb from 12 controls vs. 47 Mexico City children and young adults average age 33.06±4.8 SE years. Inductively coupled plasma mass spectrometry (metal analysis) and real time PCR (for COX2, IL1β and DNA repair genes) in target tissues. Mexico City residents had higher concentrations of metals associated with PM: manganese (p=0.003), nickel and chromium (p=0.02) along with higher frontal COX2 mRNA (p=0.008) and IL1β (p=0.0002) and COX2 (p=0.005) olfactory bulb indicating neuroinflammation. Frontal metals correlated with olfactory bulb DNA repair genes and with frontal and hippocampal inflammatory genes. Frontal manganese, cobalt and selenium increased with age in exposed subjects. Together, these findings suggest PM-metal neurotoxicity causes brain damage in young urbanites, the olfactory bulb is a target of air pollution and participates in the neuroinflammatory response and since metal concentrations vary significantly in Mexico City urban sub-areas, place of residency has to be integrated with the risk for CNS detrimental effects particularly in children.
authors.affiliation: Instituto Nacional de Pediatría, Mexico City 04530, Mexico. lilian.calderon-garciduenas@umontana.edu
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.forename: Alejandro
authors.initials: A
authors.lastname: Serrano-Sierra
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.forename: Donna
authors.initials: D
authors.lastname: Smith
authors.forename: Ricardo
authors.initials: R
authors.lastname: Delgado-Chávez
authors.forename: Janet V
authors.initials: JV
authors.lastname: Cross
authors.forename: Humberto
authors.initials: H
authors.lastname: Medina-Cortina
authors.forename: Michael
authors.initials: M
authors.lastname: Kavanaugh
authors.forename: Tomás R
authors.initials: TR
authors.lastname: Guilarte
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004784:Environmental Monitoring; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019216:Metals, Heavy / Q000493:pharmacokinetics / Q000633:toxicity*; D008800:Mexico; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D013054:Spectrophotometry, Atomic; D014018:Tissue Distribution; D014505:Urban Population; D014507:Urbanization; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D019216:Metals, Heavy