Traffic-derived air pollution and brain health: An integrative in vitro screening approach to study the neurotoxicity of ultrafine particles

Abstract

Traffic is a crucial contributor to urban air pollution, an environmental risk factor for a wide range of diseases, including neurological disorders. Ultrafine particles (UFP) consist of solid (non-volatile) and liquid (semi-volatile) particles with an aerodynamic diameter of ≤0.1 µm. Due to their small size, UFP can cross biological barriers, e.g., the lung epithelium, and they thus have the potential to reach and harm secondary target organs including the brain. To date, little is known about the possible effects of exposure to UFP on brain health and function and to what extent UFP has unique features that are not well covered by regulating PM10 an PM2.5. In addition, identifying which fractions of the UFP mixture are most hazardous may guide engineers and regulators to develop strategies that reduce negative health impact and can be used to evaluate the effectiveness of guideline levels to protect human health. Therefore, the research presented in this thesis was centered around the main aim to study the neurotoxic hazards of UFP, to identify the most hazardous components of UFP, and to understand the impact of fuel alternatives to reduce the hazard of UFP. We explored the applicability of microelectrode array (MEA) recordings using rat primary cortical cells for neurotoxicity testing of UFP. Moreover, we applied a novel approach to study the neurotoxicity of UFP upon simulated inhalation exposure in vitro by combining an air-liquid interface (ALI) cultured lung model with MEA recordings in cortical cultures for neurotoxicity screening. In summary, this thesis demonstrates that nanomaterials and UFP reduce neurotoxic hazard. However, the neurotoxic potency of traffic-derived UFP is impacted by factors affecting the chemical composition of the UFP including emission source, generation and sampling conditions, and atmospheric aging. Moreover, while MEA recordings of rat primary cortical cultures are suitable for studying the impact of nanomaterials and UFP on neuronal function, crucial elements relevant for neuroinflammation and neurodegeneration are missing in our test model. Moreover, our data suggest that combining in vitro is a promising approach to investigate systemic exposure effects, however, further development and effort are needed to capture the complexity of the whole organism in vitro.