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Title: Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.

Authors: Levesque, Shannon; Surace, Michael J; McDonald, Jacob; Block, Michelle L

Published In J Neuroinflammation, (2011)

Abstract: Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood.We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology.Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 ýýg PM/mýý) by inhalation over 6 months.DE exposure resulted in elevated levels of TNFýý at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 ýýg PM/mýý significantly increased brain TNFýý levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1ýý at only high concentrations, and a decrease in MIP-1ýý expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aýý42 levels were the highest in the frontal lobe of mice exposed to 992 ýýg PM/mýý and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 ýýg PM/mýý) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. ýý Synuclein levels were elevated in the midbrain in response to the 992 ýýg PM/mýý exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology.Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.

PubMed ID: 21864400 Exiting the NIEHS site

MeSH Terms: Air Pollutants/toxicity*; Air Pollution*; Animals; Biological Markers/metabolism*; Brain*/drug effects; Brain*/immunology; Brain*/pathology; Chemokines/metabolism; Cytokines/metabolism; Encephalitis*/chemically induced; Encephalitis*/immunology; Humans; Inhalation Exposure; Male; Neurodegenerative Diseases*/chemically induced; Neurodegenerative Diseases*/immunology; Neurodegenerative Diseases*/pathology; Rats; Rats, Inbred F344; Vehicle Emissions/toxicity*; alpha-Synuclein/metabolism; tau Proteins/metabolism

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