Subacute inhalation of ultrafine particulate matter triggers inflammation without altering amyloid beta load in 5xFAD mice.

Abstract

Epidemiological studies reveal that air pollution exposure may exacerbate neurodegeneration. Ultrafine particles (UFPs) are pollutants that remain unregulated in ambient air by environmental agencies. Due to their small size (<100 nm), UFPs have the most potential to cross the bodily barriers and thus impact the brain. However, little information exists about how UFPs affect brain function. Alzheimer's disease (AD) is the most common form of dementia, which has been linked to air pollutant exposure, yet limited information is available on the mechanistic connection between them. This study aims to decipher the effects of UFPs in the brain and periphery using the 5xFAD mouse model of AD. In our study design, AD mice and their wildtype littermates were subjected to 2-weeks inhalation exposure of UFPs in a whole-body chamber. That subacute exposure did not affect the amyloid-beta accumulation. However, when multiple cytokines were analyzed, we found increased levels of proinflammatory cytokines in the brain and periphery, with a predominant alteration of interferon-gamma in response to UFP exposure in both genotypes. Following exposure, mitochondrial superoxide dismutase was significantly upregulated only in the 5xFAD hippocampi, depicting oxidative stress induction in the exposed AD mouse group. These data demonstrate that short-term exposure to inhaled UFPs induces inflammation without affecting amyloid-beta load. This study provides a better understanding of adverse effects caused by short-term UFP exposure in the brain and periphery, also in the context of AD.

• Authors: Liudmila Saveleva, Petra Vartiainen, Veronika Górová, Sweelin Chew, Irina Belaya, Henna Konttinen, Martina Zucchelli, Paula Korhonen, Emma Kaartinen, Miika Kortelainen, Heikki Lamberg, Olli Sippula, Tarja Malm, Pasi I Jalava, Katja M Kanninen
• Journal: Neurotoxicology (Neurotoxicology) Vol. 89 Pg. 55-66 (03 2022) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 34999154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 University of Eastern Finland. Published by Elsevier B.V. All rights reserved.

Chemical References

• Air Pollutants
• Amyloid beta-Peptides
• Particulate Matter

Topics

• Air Pollutants (toxicity)
• Amyloid beta-Peptides
• Animals
• Inflammation (chemically induced)
• Inhalation Exposure (adverse effects, analysis)
• Mice
• Particle Size
• Particulate Matter (toxicity)