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

Abstract：

BACKGROUND: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. OBJECTIVE: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. METHODS:Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months. RESULTS:DE exposure resulted in elevated levels of TNFα 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 μg PM/m³ significantly increased brain TNFα 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-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m³ and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m³) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m³ exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. CONCLUSIONS: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.

journal_name

J Neuroinflammation

journal_title

Journal of neuroinflammation

authors

Levesque S,Surace MJ,McDonald J,Block ML

doi

10.1186/1742-2094-8-105

subject

Has Abstract

pub_date

2011-08-24 00:00:00

pages

105

issn

1742-2094

pii

1742-2094-8-105

journal_volume

pub_type

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