title: Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults.
abstract: Air pollution exposures have been linked to neuroinflammation and neuropathology. Autopsy samples of the frontal cortex from control (n = 8) and pollution-exposed (n = 35) children and young adults were analyzed by RT-PCR (n = 43) and microarray analysis (n = 12) for gene expression changes in oxidative stress, DNA damage signaling, NFκB signaling, inflammation, and neurodegeneration pathways. The effect of apolipoprotein E (APOE) genotype on the presence of protein aggregates associated with Alzheimer's disease (AD) pathology was also explored. Exposed urbanites displayed differential (>2-fold) regulation of 134 genes. Forty percent exhibited tau hyperphosphorylation with pre-tangle material and 51% had amyloid-β (Aβ) diffuse plaques compared with 0% in controls. APOE4 carriers had greater hyperphosphorylated tau and diffuse Aβ plaques versus E3 carriers (Q = 7.82, p = 0.005). Upregulated gene network clusters included IL1, NFκB, TNF, IFN, and TLRs. A 15-fold frontal down-regulation of the prion-related protein (PrP(C)) was seen in highly exposed subjects. The down-regulation of the PrP(C) is critical given its important roles for neuroprotection, neurodegeneration, and mood disorder states. Elevation of indices of neuroinflammation and oxidative stress, down-regulation of the PrP(C) and AD-associated pathology are present in young megacity residents. The inducible regulation of gene expression suggests they are evolving different mechanisms in an attempt to cope with the constant state of inflammation and oxidative stress related to their environmental exposures. Together, these data support a role for air pollution in CNS damage and its impact upon the developing brain and the potential etiology of AD and mood disorders.
authors.affiliation: Instituto Nacional de Pediatría, Mexico City, Mexico. lilian.calderon-garciduenas@umontana.edu
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.forename: Michael
authors.initials: M
authors.lastname: Kavanaugh
authors.forename: Michelle
authors.initials: M
authors.lastname: Block
authors.forename: Amedeo
authors.initials: A
authors.lastname: D'Angiulli
authors.forename: Ricardo
authors.initials: R
authors.lastname: Delgado-Chávez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.forename: Angelica
authors.initials: A
authors.lastname: González-Maciel
authors.forename: Rafael
authors.initials: R
authors.lastname: Reynoso-Robles
authors.forename: Norma
authors.initials: N
authors.lastname: Osnaya
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Villarreal-Calderon
authors.forename: Ruixin
authors.initials: R
authors.lastname: Guo
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Hua
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Philippe
authors.initials: P
authors.lastname: Diaz
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000397:Air Pollution / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015536:Down-Regulation; D004660:Encephalitis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D053263:Gene Regulatory Networks; D006801:Humans; D007223:Infant; D008297:Male; D008800:Mexico; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000378:metabolism*; D055815:Young Adult; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D011328:Prions; D016875:tau Proteins