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 #
1R21AG040683-01
Application #
8177379
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Wise, Bradley C
Project Start
2011-09-01
Project End
2013-06-30
Budget Start
2011-09-01
Budget End
2012-06-30
Support Year
1
Fiscal Year
2011
Total Cost
$199,260
Indirect Cost
Name
University of Southern California
Department
Type
Other Domestic Higher Education
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Cacciottolo, M; Wang, X; Driscoll, I et al. (2017) Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models. Transl Psychiatry 7:e1022
Cacciottolo, M; Morgan, T E; Finch, C E (2016) Rust on the Brain from Microbleeds and Its Relevance to Alzheimer Studies: Invited Commentary on Cacciottolo Neurobiology of Aging, 2016. J Alzheimers Dis Parkinsonism 6:
Finch, Caleb E; Shams, Sara (2016) Apolipoprotein E and Sex Bias in Cerebrovascular Aging of Men and Mice. Trends Neurosci 39:625-37
Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra et al. (2016) The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice. Neurobiol Aging 37:47-57
Cheng, Hank; Saffari, Arian; Sioutas, Constantinos et al. (2016) Nanoscale Particulate Matter from Urban Traffic Rapidly Induces Oxidative Stress and Inflammation in Olfactory Epithelium with Concomitant Effects on Brain. Environ Health Perspect 124:1537-1546
Cheng, Hank; Davis, David A; Hasheminassab, Sina et al. (2016) Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNF? in vitro. J Neuroinflammation 13:19
Finch, Caleb E; Austad, Steven N (2015) Commentary: is Alzheimer's disease uniquely human? Neurobiol Aging 36:553-5
Woodward, Nicholas; Finch, Caleb E; Morgan, Todd E (2015) Traffic-related air pollution and brain development. AIMS Environ Sci 2:353-373
Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M (2014) Uneven futures of human lifespans: reckonings from Gompertz mortality rates, climate change, and air pollution. Gerontology 60:183-8
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

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