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Serotonin Expression in the Airway Epithelium of Postnatal Rhesus Monkeys: Effect of Ozone or House Dust Mite Antigen (HDMA) ExposureEPA Grant Number: FP917122
Title: Serotonin Expression in the Airway Epithelium of Postnatal Rhesus Monkeys: Effect of Ozone or House Dust Mite Antigen (HDMA) Exposure
Investigators: Murphy, Shannon Renee
Institution: University of California - Davis
EPA Project Officer: Boddie, Georgette
Project Period: September 1, 2010 through August 31, 2013
Project Amount: $111,000
RFA: STAR Graduate Fellowships (2010) RFA Text | Recipients Lists
Research Category: Academic Fellowships , Fellowship - Human Health: Risk Assessment and Decision Making
Evidence supports that air pollutants such as ozone exacerbate asthma symptoms and children represent a particularly sensitive population. This research project will use an animal model of childhood asthma to define how effects of ozone exposure during postnatal lung development change serotonin/receptor expression, potentially enhancing airway hyperresponsiveness.
Ozone is a major component of air pollution that worsens childhood asthma. Exposure to unhealthful levels of ozone poses a health concern for children, a group more vulnerable than adults to poor air quality as their lungs are not yet fully developed. This project examines the role of serotonin, a key nerve chemical, in air pollution-driven asthma exacerbation in children. Ultimately, this work may identify new targets for disease treatment.
This research takes advantage of an established rhesus monkey model of postnatal airway development and allergic airway disease to further examine how exposure to house dust mite antigen (HDMA) and ozone during early postnatal development leads to altered afferent (sensory) and efferent nerve-tissue interactions that may contribute to deficiencies in pulmonary function and increased airway reactivity. This project focuses on changes in receptors and ligands normally associated with neural function and will be executed in three parts. First, we will define the normal development pattern of serotonin and serotonin receptor distribution by airway level and increasing age of the postnatal Rhesus monkey model through immunohistochemically based morphometric approaches. Second, we will compare serotonin and serotonin receptor patterns in the epithelium and interstitium of normal versus exposed animals, defining serotonin sequestration among four key lung cell types. Finally, we will examine postnatal airway exposure history to evaluate responses to neurokinin receptor-mediated acute oxidant stress. Ultimately, these specific aims seek to define the presence of serotonin and its potential modulatory activities in neural and immunological interactions within the lung.
This project seeks to examine the overall question of how episodic exposure to allergens or oxidative pollutants during the critical window of postnatal development results in serotonin/receptor expression changes that may participate in the development of hyperresponsive airways. We hypothesize that the abundance of serotonin in normal lung will decrease with postnatal age and that its expression in airway epithelium will be associated with specific airway regions. Exposure to inhaled pollutants may increase the abundance of serotonin with postnatal age and can also change the cell type and airway level distribution profile. We hypothesize that exposure to inhaled pollutants alters the response to oxidative stress, making airways more vulnerable to injury. We postulate that developmental deviations are exacerbated when immune functions are altered due to antigenic exposure and, when combined with oxidative stress from the air pollutant ozone, result in development of a sensitive phenotype.
Potential to Further Environmental/Human Health Protection:
This research further investigates why a key subpopulation is more sensitive to a known environmental pollutant and ultimately facilitates pulmonary health risk assessment for children living in polluted areas. Additionally, this work more clearly defines the adverse developmental consequences of exposure to air pollution during childhood that may present greater, and potentially irreversible, health problems throughout the life of the individual.