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NANOMETER DIESEL EXHAUST PARTICLES ARE NEUROTOXIC TO DOPAMINERGIC NEURONS THROUGH MICROGLIAL ACTIVATION.
Citation:
Block, M. L., X. Wu, P. Zhong, G. Li, T. Wang, J. S. Hong, AND B Veronesi. NANOMETER DIESEL EXHAUST PARTICLES ARE NEUROTOXIC TO DOPAMINERGIC NEURONS THROUGH MICROGLIAL ACTIVATION. Presented at Society for Neuroscience, New Orleans, LA, 11/8-12/03.
Description:
NANOMETER DIESEL EXHAUST PARTICLES ARE NEUROTOXIC TO DOPAMINERGIC NEURONS THROUGH MICROGLIAL ACTIVATION. M.L. Block1,2, X. Wu1, P. Zhong1, G. Li1, T. Wang1, J.S. Hong1 & B.Veronesi.2
1The Laboratory of Pharmacology and Chemistry, NIEHS, RTP, NC and 2 National Health and Environmental Effects Research Laboratory, USEPA, RTP, NC.
The role of environmental factors in the development of neurodegenerative diseases is becoming increasingly evident. Recently, it has been reported that components of air pollution known as ?particulate matter? (PM) are able to traverse the blood-brain barrier and have been discovered in the brain. While PM-induced oxidative stress has been associated with an increased incidence of cardiovascular and respiratory disease, the effects on the central nervous system have yet to be defined. In this study, we report that nanometer-size diesel emission particles (< 0.22 ?m) (DEP) are neurotoxic to dopaminergic (DA) neurons and that this toxicity is mediated through microglia. Specifically, mesencephalic neuron-glia cultures treated with DEP (5-50 ?g/ml) showed a dose-dependent decrease in DA neurons. The importance of glia was demonstrated by the failure of neuron-enriched cultures to exhibit DEP-induced DA neurotoxicity. Analysis of DEP-treated neuron-glia cultures showed no increase in pro-inflammatory factors such as, NO, TNF?, or PGE2. However, superoxide was produced from enriched-microglia cultures derived from P1 rat pups in response to DEP. Also, enriched-microglia cultures treated with DEP demonstrated a dose dependent increase in intracellular reactive oxygen species. Immunocytochemical analysis with the microglia specific antibody, OX42, on DEP-treated neuron-glia cultures at 9 days post treatment revealed distinct activated microglia morphology that was unique to DEP. In summary, these data suggest that DEP specifically kills DA neurons through the activation of microglia. (This abstract has been reviewed by NHEERL but does not necessarily reflect EPA policy)