Air pollution may accelerate brain aging. Epidemiological studies of the middle-age have shown accelerated cognitive decline in association with local differences in air pollution (Chen &Schwartz 2010), while brains of young adults from a highly polluted Mexican city had premature deposits of diffuse amyloid and glial inflammatory activation which were greater in apoE4 carriers (Block &Calderon-Garciduenas 2009). Corresponding rodent models with defined exposure to traffic-generated nano-sized particulate material (nPM) have shown glial inflammatory changes. Our pilot data show that exposure to nPM for 10 weeks activated glia and altered neuronal glutamatergic receptors in vivo and in vitro. We propose to analyze effects of nPM on glial inflammation, amyloidogenesis, and neurodegeneration in J20-ADtg mice and in triple transgenic AD mice (3xTg-AD), which has more extensive AD-like neuropathology. We will also test the hypotheses that nPM promotes Abeta42 production and exacerbates Abeta42-induced toxicity using in vitro models.

Public Health Relevance

These novel studies will use mouse models to define the neurodegenerative pathways of urban airborne nano-sized particulate matter (nPM). We will evaluate the hypothesis that nPM causes neural damage through shared pathways with amyloid-beta. Identification of mechanisms and of relevant biomarkers in nPM toxicology is essential for development of broad-spectrum interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG040683-02
Application #
8321503
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Wise, Bradley C
Project Start
2011-09-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$166,050
Indirect Cost
$63,550
Name
University of Southern California
Department
None
Type
Other Domestic Higher Education
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Davis, David A; Bortolato, Marco; Godar, Sean C et al. (2013) Prenatal exposure to urban air nanoparticles in mice causes altered neuronal differentiation and depression-like responses. PLoS One 8:e64128
Davis, David A; Akopian, Garnik; Walsh, John P et al. (2013) Urban air pollutants reduce synaptic function of CA1 neurons via an NMDA/N? pathway in vitro. J Neurochem 127:509-19
Zhang, Hongqiao; Liu, Honglei; Davies, Kelvin J A et al. (2012) Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments. Free Radic Biol Med 52:2038-46