Subacute Inhalation of Ultrafine Particulate Matter Triggers Inflammation Without Altering Amyloid Beta Load in 5xFAD mice.
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 (<100nm), 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. Alzheimers 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 blood-brain barrier integrity or 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. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/459017v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@479511org.highwire.dtl.DTLVardef@18bc59aorg.highwire.dtl.DTLVardef@15a0240org.highwire.dtl.DTLVardef@49f911_HPS_FORMAT_FIGEXP M_FIG C_FIG