Dissertation

Olfactory Uptake of Inhaled Nanoparticle Aerosols – an Examination of Uptake, Transport, and Fate in the Upper Respiratory Tracts of Mice

Hopkins, Laurie Ellen

2012

Overview

Polluted air commonly contains suspended particulate matter (PM), including large numbers of particles in the ultrafine or nano size fraction. Epidemiological and toxicological research indicates an association between the particulate component of air pollution and adverse respiratory and cardiovascular health effects in humans. The relationship between airborne particles and the observed health effects is not yet well understood mechanistically, although particle size and chemical composition appear to be critical factors conferring potential toxicity. We hypothesized that inhaled particulate of sufficiently small size could contribute to the observed health effects by entering the brain via olfactory nerve tracts and provoking a pro-inflammatory response in targeted tissues. To investigate the hypothesis, we undertook a series of experiments in which mice were briefly exposed to nanoparticle aerosols. In separate experiments, mice were exposed to aerosols of ultrafine iron oxide (Fe2O 3) or CdSe-ZnS nanocrystals (quantum dots). Following exposure, respiratory tract and central nervous system tissues were examined for the presence of these particles and exposure-related biological responses. Olfactory-derived primary cell cultures also were exposed to quantum dots. Particles were detected using a combination of techniques including standard and fluorescent light microscopy, electron microscopy, and elemental analysis. Responses were measured using histochemical and biochemical methods. In mice exposed to ultrafine iron oxide aerosols, we found evidence of particle uptake and pro-inflammatory responses in the lung and the olfactory bulb. In mice exposed to quantum dot aerosols, we found evidence of particle uptake and pro-inflammatory responses in the olfactory bulb. Uptake was more pronounced for quantum dots than iron, with quantum dots detected in olfactory bulbs less than three hours post-exposure. Electron microscopy revealed quantum dots within axons of the olfactory nerve tracts connecting the nasal mucosa to the olfactory bulbs. Following in vitro exposure, we found evidence of selective uptake of quantum dots by distinct subpopulations of cells. In mixed glia-neuron cultures, particle uptake was most prominent in microglia, while in olfactory epithelial cultures particle uptake was essentially limited to unidentified cells morphologically similar to olfactory stem cells. Our results clearly demonstrate that inhaled particles can enter the brain via olfactory nerves.

• Publisher: ProQuest Dissertations Publishing
• Subject: Nanoscience / Pharmacology / Surgery / Toxicology
• ISBN: 9781267968418, 1267968419