|Title||Air pollution neurotoxicity throughout the lifespan: studies on the mechanism of toxicity and interactions with effects of sex and genetic background.|
|Year of Publication||2020|
|Degree||Biology of Aging|
|University||University of Southern California|
|Keywords||Air Pollution, genetic, neurotoxicity, Sex Characteristics, Sex differences|
Air pollution (AirP) is a leading global environmental risk factor of mortality and morbidity in humans and many other organisms. AirP affects the lives of more than 90% of the humans from all ages and unfortunately has an increasing trend in developing countries. Depends on the life stage, exposure to AirP can increase the risk of neurodevelopmental or neurodegenerative diseases. Alarmingly, lack of understanding of the AirP toxicity mechanisms likely led to a severe underestimation of the global health burden of these complex toxicants. AirP toxicity is shaped by a complex interface of chemical properties of toxicants mixture and the biological features of the exposed individuals (e.g. genetic structure, sex, and life-stage). The current dissertation is comprised of a series of projects to resolve some of these complex interactions. In chapters 2-3, we discussed how the chemical characterization of AirP can alter the neurotoxicity in vivo and in vitro. Moreover, we developed a cell-based assay that can predict the neurotoxicity of the AirP particulate matter (PM) in the brain. Chapters 4-7 approaches the nuances in the molecular toxicity of AirP between different life stages (development vs adult), sexes (males vs females), and some genetic variants (ApoE3 vs ApoE4). We also corroborated our findings in Caenorhabditis elegans, a known nematode model for aging research. In the last chapter, we described the gender differences in vulnerability to life-time cigarette smoke exposure for some aging-associated health outcomes. Throughout the dissertation, we discussed the facing challenges in the AirP toxicology field, and also identified potential molecular mechanisms that underlay each complex research question. We hope that our findings lead to several novel studies and translate into the regulation soon.