Amy R. Mackos, United States of America
Ohio State University College of NursingAuthor Of 1 Presentation
PARTICULATE MATTER EXPOSURE EXACERBATES Aβ PLAQUE DEPOSITION AND GLIOSIS IN APP/PS1 MICE
Abstract
Aims
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and neuronal death. There are several well-established genetic and environmental factors hypothesized to contribute to AD pathology and progression. One such factor is air pollution. However, the molecular mechanisms by which air pollution exacerbates AD are not well understood. This study was designed to explore the effects of particulate matter exposure on AD-related brain changes using the APP/PS1 transgenic model of the disease.
Methods
Male C57BL/6;C3H wild type and APP/PS1mice, were exposed to either filtered air (FA) or particulate matter sized under 2.5 μm (PM2.5) for 6 h/day, 5 days/week for 3 months, and brains were collected. Immunohistochemistry for Aβ, GFAP, Iba1, and CD68 was performed on fixed brain sections. Aβ ELISAs and cytokine arrays were performed on frozen hippocampal and cortical lysates, respectively.
Results
The Aβ plaque load was significantly increased in the hippocampus of PM2.5 exposed APP/PS1 mice compared to their respective FA controls. Additionally, in the PM2.5 exposed APP/PS1 group, increased astrocytosis and microgliosis were observed as indicated by elevated GFAP, Iba1, and CD68 immunoreactivities. The cytokines TNF-α, IL-6, IL-1β, IFN-γ, and MIP-3α were also elevated in the cortices of PM2.5 exposed APP/PS1 mice compared to FA controls.
Conclusions
Our data suggest that chronic particulate matter exposure exacerbates AD by increasing Aβ plaque load, gliosis, and brain inflammatory status.