Respiratory infections and irritant exposures have been shown to increase neurotrophin levels in the airways, and increased neurotrophin levels have been shown to cause a hyperinnervation of the airways. However, the possibility that the increase in innervation is due to an increased survival of neurons innervating the airways has not yet been determined. The goal of this research is to establish if increased neurotrophin levels in the airways during periods of normally occurring postnatal cell death will cause an increase in the survival of sensory neurons innervating the tracheal epithelium, resulting in an increased nerve fiber density of the epithelium. To better characterize the role that neurotrophins play;neurons that specifically innervate the airway will be quantified, the nerve fiber density of the tracheal epithelium will be determined, and the gene expression nerve growth factor (NGF) will be examined throughout normal postnatal development. In addition, neurotrophin action in the airways will be inhibited and the same parameters explored. Finally, airway development will be assessed following an acute ozone exposure during the period of normally occurring postnatal cell death. Animals will be examined between postnatal days 6 and 60 so that changes in airway neural sensory development can be ascertained. It will also be determined if differences between the sexes exist. The techniques that will be employed to complete this work include, Laser Capture Microdissection, Real-Time PCR, design based stereology, and immunohistochemistry. Childhood asthma is a growing concern in major cities around the world. Understanding how the airways change during development and how they are affected by exposures to environmental air pollutants, such as ozone is becoming of greater concern. The research proposed in this application will work towards determining what changes are occurring and if Nerve Growth Factor released in the airways following ozone exposures is responsible for these changes.
