Air pollutants derived from fossil fuels are recognized for accelerating arterial and pulmonary diseases. Moreover, brain dysfunctions during development and aging have been associated with air pollutants by postmortem findings on young humans (Block &Calderon-Garciduenas 2009) and by epidemiologic studies of the middle-aged (Chen &Schwartz 2009). Correspondingly, young rodents show glial inflammatory changes with defined exposure to traffic-generated nano-sized PM (nPM) (Zanchi et al 2010;Kleinman et al 2008). Our pilot data show effects of nPM on neuronal glutamatergic receptors in vivo and in vitro. We propose to analyze age and gender interactions in neurodegenerative effects of nPM in young adult and middle-aged C57BL/6 mice, using re-aerosolized nPM from urban Los Angeles.
Aim 1 will expose animals to re-aerosolized nPM for 20 weeks, with assessment of memory, and neuronal and glial functions.
Aim 2 will evaluate in vitro glial age effects on neuronal activities in response to aqueous suspensions of nPM.

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 of inflammation and oxidative stress. 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 #
5R21AG040753-02
Application #
8321501
Study Section
Clinical Neuroimmunology and Brain Tumors Study Section (CNBT)
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
Cheng, Hank; Davis, David A; Hasheminassab, Sina et al. (2016) Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFα in vitro. J Neuroinflammation 13:19
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
Woodward, Nicholas; Finch, Caleb E; Morgan, Todd E (2015) Traffic-related air pollution and brain development. AIMS Environ Sci 2:353-373
Heo, Jongbae; Antkiewicz, Dagmara S; Shafer, Martin M et al. (2015) Assessing the role of chemical components in cellular responses to atmospheric particle matter (PM) through chemical fractionation of PM extracts. Anal Bioanal Chem 407:5953-63
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
Finch, Caleb E; Tower, John (2014) Sex-specific aging in flies, worms, and missing great-granddads. Cell 156:398-9
Campbell, Arezoo; Daher, Nancy; Solaimani, Parrisa et al. (2014) Human brain derived cells respond in a type-specific manner after exposure to urban particulate matter (PM). Toxicol In Vitro 28:1290-5
Li, Rongsong; Navab, Mohamad; Pakbin, Payam et al. (2013) Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice. J Lipid Res 54:1608-15
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
Chepelev, Nikolai L; Zhang, Hongqiao; Liu, Honglei et al. (2013) Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction. Redox Biol 1:183-9

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