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AMBIENT PARTICULATE MATTER STIMULATES OXIDATIVE STRESS IN BRAIN MICROGLIA AND DAMAGES NEURONS IN CULTURE.
Citation:
GILLESPIE, P., P. SAMA, J. PARKER, L. C. CHEN, AND B. VERONESI. AMBIENT PARTICULATE MATTER STIMULATES OXIDATIVE STRESS IN BRAIN MICROGLIA AND DAMAGES NEURONS IN CULTURE. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
Description:
Ambient particulate matter (PM) damages biological targets through oxidative stress (OS) pathways. Several reports indicate that the brain is one of those targets. Since microglia (brain macrophage) are critical to OS-mediated neurodegeneration, their response to concentrated ambient particles (CAPs) collected from Tuxedo, NY was examined in culture. Immortalized, mouse microglial (BV2) were exposed to CAPs for various time points. Significant increases in pro-inflammatory cytokines and reductions of glutathione were measured in these cells. Up-regulation of genes coding for apoptotic and OS were recorded using Affymetrix microarrays. To assess neurotoxicity, immortalized rat, dopaminergic neurons (N27) were exposed to Fine (F=0.18-1¿m) and Ultrafine (UF<0.18¿m) PM also collected in Tuxedo, NY. Evidence of reduced nuclear materials, as measured by Hoechst 33258 stain occurred only in response to >12.5 ¿g/ml UF and 50 ¿g/ml F after 24 hr exposures. Primary cultures, dissociated from embryonic rat brain striatum were exposed to F (75 ¿g/ml) and UF (7.5 ¿g/ml) to determine if neurotoxicity was size-dependent in complex cultures. Equivalent increases of reactive nitrogen species (nitrite) were seen after 24hr in response to both size particles in spite of their 10-fold differences in concentration. A 39% and 47% reduction of immunohistochemically stained neurons relative to controls were measured in cultures treated with F and UF, respectively. Microscopic examination revealed that the majority of PM exposed neurons were apoptotic after 24hr exposure. Together, these data indicate that PM damages isolated neurons directly and those in dissociated brain cultures, plausibly through microglia initiated apoptotic pathways. Disclaimer: This abstract has been reviewed by the NHEERL of the EPA and approved for publication. Approval does not signify that the contents reflect the views of the Agency.