This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The perinatal environment influences development of the respiratory control system in mammals and birds. We have been studying a model of developmental plasticity in which rats are exposed to hyperoxia (60% oxygen) during the first 1-4 postnatal weeks. These rats exhibit permanently attenuated ventilatory responses to acute hypoxia owing to abnormal development of the carotid body, the primary chemoreceptor that monitors arterial oxygen levels. Our project is investigating the cellular and molecular mechanisms by which elevated oxygen influences carotid body development. Experiments conducted in previous reporting periods revealed that antioxidants do not prevent changes in carotid body functional development during perinatal hyperoxia. This result is consistent with our hypothesis that hyperoxia influences carotid body development through activity-dependent pathways rather than overt cellular toxicity. Recent experiments indicate that hyperoxia alters the expression of specific genes known to regulate carotid body development, and we are currently studying additional genes of interest. Whereas most of our work has used rats as experimental models, we are also developing an avian model for studying how oxygen regulates carotid body development. Our experiments indicate that hyperoxia impairs ventilatory responses to hypoxia in quail, although the critical period during which quail are susceptible to this plasticity is at an earlier age relative to rats. Ultimately this research will provide insights into how oxygen levels regulate the normal and pathological development of the respiratory control system.
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