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
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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
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