Environmental air pollutants adversely affect cognition and cause progressive neurodegeneration through unknown mechanisms. It is known, however, that neurodegenerative disorders are associated with changes in neurogenesis. Thus, environmental air pollutants have the potential to alter neurogenesis and stem cell function, thereby causing neuronal dysfunction. To date, no investigation has examined the consequences of environmental air pollutants on neurogenesis. Emerging data link exposure to ambient air pollution and cognitive deficits in both children and adults. Children are especially sensitive to environmental pollutants and the mechanisms for this increased susceptibility have not been elucidated. In children neurogenesis takes place at a high rate in the developing brain, at a time when they are vulnerable to environmental pollutants. In addition, environmental air pollution exacerbates the progression of neurodegenerative disorders such as Alzheimer's disease in adults. Exposure to environmental air pollutants during critical periods of development and across lifespan can alter stem cell function and fate and, in so doing, induce neuronal dysfunction. As about half of the US populations (~ 154 million people) live in counties that have harmful air quality, there is an urgent need to understand the fundamental effects of environmental air pollutants on neurogenesis and stem cell function. The objective of this application is to measure the effects of exposure to real-world air pollution on neuronal stem cells using the mouse model. The central hypothesis is that ambient airborne pollutants will adversely alter neurogenesis regardless of the developmental stage. This research will utilize a unique resource to obtain real-world air pollution: the Great Lakes Air Center for Integrative Environmental Research (GLACIER) mobile research laboratory equipped for whole animal inhalation studies and atmospheric monitoring. This will allow whole animal exposure to characterized concentrated ambient fine particulate matter (PM2.5) from a multi-pollutant atmosphere commonly found in the Great Lakes Region of the United States. Neurogenesis will be examined in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. Not only do these regions continuously undergo neurogenesis, but they are also associated with cognition and neurodegenerative disorders.
The aim i s to identify developmental stages in which (1) neurogenesis and (2) progenitor cell fate are susceptible to air pollutant-induced adverse effects. This proposed exploratory project is expected to reveal that primary air pollutants are capable of eliciting multiple, important, advers changes in neurogenesis and stem cell function that are dependent on the developmental stage at the time of exposure. The expected outcome will have a positive impact on human health as it will provide insights into the response of stem cells to environmental pollutants that may alter stem cell function, stem cell fate, or the cellular composition that could predispose individuals towards disease.
Over 50% of the US population is exposed to air quality that exceeds National Ambient Air Quality Standards. Particulate air pollution has been linked to neurodegenerative disorders in which neurogenesis may be altered;however, it is not known what the effects of air pollution are on neurogenesis. The proposed research is relevant to public health because it will provide a detailed understanding of the effects of ambient airborne particulate matter on neurogenesis from the postnatal to the mature adult that is currently lacking.
