A Whole-Body Ultra-Fine Aerosol Exposure Chamber for Dynamic Detection of Alzheimer's Disease Biomarkers in Mice
JOSEPH V. PUTHUSSERY, August Li, Carla M. Yuede, John Cirrito, Rajan K. Chakrabarty,
Washington University in St.Louis Abstract Number: 532
Working Group: Health-Related Aerosols
AbstractA growing body of epidemiological studies indicates ambient particulate matter (PM) as a potential neurotoxin directly linked with the onset of Alzheimer's disease (AD). Researchers hypothesize that the chemical components present in PM, such as transition metals and carbonaceous aerosols if exposed to the brain, can induce chronic inflammation and produce reactive oxygen species that can damage the blood-brain barrier, and increase the production of amyloid-beta (Aβ; a biomarker of AD) peptides. While there is compelling evidence of a plausible association between air pollution exposure and AD, the exact mechanism of PM-induced neurotoxicity and AD remains largely unknown. While past AD mice model studies have investigated long-term exposure to air pollution, monitoring the dynamic changes in mice brain activity during acute PM exposure has remained a technological challenge.
Here, using state-of-the-art
in situ measurement techniques, we designed and developed a whole-body mice exposure chamber coupled to a microdialysis (MD)-based real-time brain interstitial fluid (ISF) Aβ peptide measurement unit. The chamber can uniquely facilitate the investigation of acute (few hours) air pollution exposure in the formation of Aβ plaques in mouse brains. It consists of a custom-designed ~160-liter acrylic enclosure connected to a test pollutant generator at user-defined concentrations. The chamber holds two mice simultaneously inside specially designed individual RaTurn cages (BASi) that permit freedom of movement and ad-lib food/water while ISF is being sampled. Microdialysis probes are surgically implanted in the mouse's hippocampus, and the MD unit measures the Aβ peptide proteins within the brain interstitial fluid in freely moving awake mice every 60 minutes for 3-5 days. The temperature, relative humidity, particle size distribution, and particle number concentrations inside the chamber are monitored using real-time sensors. Chamber characterization using aerosolized monodisperse polystyrene latex beads shows the chamber is well-constrained and provides a uniformly mixed aerosol exposure environment for the test animals. Efforts are underway to test the mice's response when exposed to different nano-size environmental pollutants. Preliminary results based on exposure to real-world relevant air pollutants such as copper, iron, and biomass-burning aerosols will be presented.