title: Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons.
abstract: Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter <2.5-μm diameter (PM2.5). Rodents exposed to TRAP have shown microglial activation and neuronal atrophy. We further investigated age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young- and middle-aged mice (3 and 18 months female C57BL/6J) were exposed to nanoscale-PM (nPM, <0.2 μm diameter). Young mice showed selective changes in the hippocampal CA1 region, with neurite atrophy (-25%), decreased MBP (-50%), and increased Iba1 (+50%), with dentate gyrus relatively unaffected. Exposure to nPM of young mice decreased GluA1 protein (-40%) and increased TNFa mRNA (10×). Older controls had age changes approximating nPM effects on young, with no response to nPM, suggesting an age-ceiling effect. The CA1 selective vulnerability in young mice parallels CA1 vulnerability in Alzheimer's disease. We propose that TRAP-associated human cognitive and white matter changes involve hippocampal responses to nPM that begin at younger ages.
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Woodward
authors.affiliation: Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: Payam
authors.initials: P
authors.lastname: Pakbin
authors.affiliation: Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: Arian
authors.initials: A
authors.lastname: Saffari
authors.affiliation: Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: Farimah
authors.initials: F
authors.lastname: Shirmohammadi
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Haghani
authors.affiliation: Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Cacciottolo
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Department of Molecular and Computational Biology, Dornsife College, University of Southern California, Los Angeles, CA, USA. Electronic address: cefinch@usc.edu.
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000473:pathology* / Q000523:psychology; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D001284:Atrophy; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D003071:Cognition; D005260:Female; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology*; D016501:Neurites / Q000187:drug effects* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D010316:Particle Size; D052638:Particulate Matter / Q000009:adverse effects*; D001335:Vehicle Emissions / Q000633:toxicity*; D066127:White Matter / Q000187:drug effects / Q000473:pathology
chemical_list: D052638:Particulate Matter; D001335:Vehicle Emissions
keywords: Aging; Air pollution; CA1; Hippocampus; Particulate matter; White matter