Research Projects

Project at a Glance

Project Status: complete

Title: Central nervous system effects of ambient particulate matter: the role of oxidative stress and inflammation

Principal Investigator / Author(s): Kleinman, Michael

Contractor: UC Irvine

Contract Number: 08-306

Research Program Area: Health & Exposure

Topic Areas: Health Effects of Air Pollution


The objective of this project was to determine how the biological responses in the brains of apoE-/- mice exposed to fine PM (PM that is 2.5 microns or less in diameter, PM2.5) might depend on the composition of ambient PM emitted from vehicles, power generation, industrial processes and other sources. Brain tissue from mice exposed to concentrated ambient fine particles (CAPs) was obtained by collaborative agreements from a multicity study that was part of an ongoing program sponsored by the Health Effects Institute and conducted by Dr. Morton Lippmann and his colleagues at New York University (NYU). Mice were exposed in New York City (NYC), Sterling Forest, NY (SF), Seattle, WA (SEA), East Lansing, MI (MSU) and Irvine, CA (UCI). Exposures were 6 hours per day, 4 days per week for 26 weeks (6 months). Brains were harvested and analyzed for inflammatory cytokines (Interleukin-6, Interleukin-10 and Tumor Necrosis Factor-α), reduced and oxidized glutathione, as markers for anti-oxidant defenses, and biomarkers of oxidative stress (protein carbonyls, hydroxynonenal and malondialdehyde). Particulate samples from the exposure atmosphere were collected and analyzed for mass concentration, elemental and organic carbon contents and trace metal composition. The component data were used in a source apportionment analysis to identify the key sources that contributed to the PM2.5 at each of the five locations. While the analysis of the trace component composition and the source apportionment determinations provided useful confirmation of the a priori criteria used for selecting the exposure locations used in this study, differences in exposure concentrations, times of study and differences in the efficiency of operation of the VACEs between the five locations made it difficult to draw strong conclusions about source contribution influences on brain outcomes. This study demonstrated that exposure of apoE-/- mice to CAPs was associated with inflammatory changes in the brain, and that on a regional basis, the sections of the brain that were lower in the signal transducer nuclear factor-ĸB (NF-ĸB) tended to be more susceptible to inflammatory changes. In addition the levels of NF-ĸB decreased as the animals aged during the 6 month study in both Filtered Air (FA) and CAPs-exposed mice. Sections of the brain with lower NF-ĸB levels also tended to exhibit exposure-related increases in concentrations of biomarkers of oxidative stress, consistent with a correlation between inflammation and oxidative changes in the brain. Oxidative changes in the brain were consistently observed in mice exposed at SEA but not in mice exposed at MSU. Mice exposed at UCI showed a pattern of changes that was the same as that seen in SEA mice but because the UCI brains had been sectioned for brain regional analysis, the variances were larger in the UCI group than in the SEA group and the average effect differences compared to FA-exposed brains did not achieve statistical significance. The sources of PM at the UCI and SEA sites were more influenced by emissions related to oil combustion (such as motor vehicles, power generation, space heating) than was the PM at the MSU site, as evidenced by a high correlation of PM concentrations with the concentrations of Ni and V in the particles at UCI and SEA but not at MSU. The concentrations of Ni and V in the exposure atmosphere were probably too low to be directly toxic and it is likely that these elements are tracers or surrogates for oil combustion aerosols which would include EC, OC and BC. The pattern of more exposure-related increases in oxidative stress markers at SEA and UCI relative to MSU could indicate that the products of oil combustion from mobile, power generation and space heating sources may be important factors in the inflammatory and oxidative changes noted in the brains of apoE-/- mice exposed to CAPs.


For questions regarding this research project, including available data and progress status, contact: Heather Choi at (916) 322-3893

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