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

TLDR

Air pollution is increasingly linked to neuroinflammation and neuropathology, yet the long‑term exposure effects remain poorly understood. The study aimed to determine the CNS effects of subchronic diesel exhaust exposure and the lowest concentrations that trigger neuroinflammation and early neuropathology markers. Six‑month inhalation of diesel exhaust at concentrations ranging from 0 to 992 μg PM/m³ was administered to male Fischer 344 rats. Diesel exhaust exposure elevated TNFα in most brain regions, with the midbrain most sensitive even at 100 μg PM/m³, while other inflammatory markers varied; high‑dose exposure also increased Alzheimer‑ and Parkinson‑related proteins (Aβ42, tau pS199, α‑synuclein) mainly in the midbrain, indicating that neuroinflammation may precede early neurodegenerative markers at high pollution levels.

Abstract

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/m 3 ) 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/m 3 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/m 3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m 3 ) 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/m 3 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.